In several human malignancies, the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival. RCAS1 alters the tumor microenvironment by inducing peripheral lymphocyte apoptosis and angiogenesis, while reducing the vimentin-positive cell population. Although proteolytic processing, referred to as “ectodomain shedding,” is pivotal for induction of apoptosis by RCAS1, the proteases involved in RCAS1-dependent shedding remain unclear. Here we investigated proteases involved in RCAS1 shedding and the association between tumor protease expression and serum RCAS1 concentration in uterine cancer patients. A disintegrin and metalloproteinase (ADAM) 9 was shown to be involved in the ectodomain shedding of RCAS1. Given the significant correlation between tumor ADAM9 expression and serum RCAS1 concentration in both cervical and endometrial cancer as well as the role for ADAM9 in RCAS1 shedding, further
Recombinant Human Tumor-associated Calcium Signal Transducer 2/TROP-2 (C-Fc)|| Human Tumor-associated Calcium Signal Transducer 2/TROP-2 (C-Fc)|| Tumor-associated Calcium Signal Transducer 2/TROP-2 (C-Fc)
The human 5T4 oncofoetal antigen is expressed by all types of trophoblast in pregnancy but is not detected on most adult tissues, although low levels are found on some epithelia. However, this antigen is strongly expressed by many cancers and tumour-associated labelling correlates with metastatic spread and poor clinical outcome for patients with gastric and colon cancer. Over-expression of the gene influences cell adhesion, shape and motility, which may be related to changes in the cellular localisation of the 5T4 oncofoetal antigen as malignancy develops. To establish whether the 5T4 oncofoetal antigen can serve as a tumour-specific marker for oral cancer and precancer, we have evaluated the pattern of expression on biopsies of normal, inflamed and dysplastic oral mucosa using immunohistochemistry. Oral mucosa, taken from different sites in the mouth, expressed the 5T4 oncofoetal antigen with varying intensity and pattern. The majority of the immunoreactivity was detected in the basal and ...
BioMed Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies covering a wide range of subjects in life sciences and medicine. The journal is divided into 55 subject areas.
The biologic and clinical significance of the oncofetal antigens carcinoembryonic antigen (CEA) and alpha1-fetoprotein (AFP) are discussed. Although the current assays for these molecules are not tumor-specific, measurement of these molecules in the circulation of cancer patients is useful either for tumor diagnosis or for management of the cancer patient in the postoperative or post-chemotherapy state. An approach to increasing the specificity of the CEA radioimmunoassay is described. ...
Haughton, G; Lanier, L L.; Babcock, G F.; Lynes, D M.; and willexploit, N., Ation of the surface idiotype as tumor specific antigen. (1978). Subject Strain Bibliography 1978. 2066 ...
Liang, W and Cohen, E P., Detection of thymus leukemia antigens on the surface membranes of murine leukemia cells resistant to thymus leukemia anti- bodies and guinea pig complement. (1977). Subject Strain Bibliography 1977. 2311 ...
As a leading supplier of innovative life science research tools, Creative Diagnostics continues to expand its products portfolio by offering of unique antigens for researchers globally, which is supported by extensive research, development, and validation for superior quality. The addition of antigen products and services will enable scientists to work on more specific projects, and also provide leading researchers and diagnostic manufacturers with a more diverse antigen selection, which facilitates the development of assays with greater specificity and sensitivity.. These newly released antigens are rigorously tested to meet the demand in research and development and are featured with excellent quality, including Viral Antigens, Bacterial Antigens, Fungal Antigens, Parasitic Antigens, Immunoglobulin, Hapten, Cardiac Biomarkers and so on. With this expanded offering of antigens products, Creative Diagnostics enables scientists to achieve more complete analysis experiments. These products along ...
Many patients develop tumor antigen-specific T cell responses detectable in peripheral blood mononuclear cells (PBMCs) following cancer vaccine. However, measurable tumor regression is observed in a limited number of patients receiving cancer vaccines. There is a need to re-evaluate systemically the immune responses induced by cancer vaccines. Here, we established animal models targeting two human cancer/testis antigens, NY-ESO-1 and MAGE-A4. Cytotoxic T lymphocyte (CTL) epitopes of these antigens were investigated by immunizing BALB/c mice with plasmids encoding the entire sequences of NY-ESO-1 or MAGE-A4. CD8(+) T cells specific for NY-ESO-1 or MAGE-A4 were able to be detected by ELISPOT assays using antigen presenting cells pulsed with overlapping peptides covering the whole protein, indicating the high immunogenicity of these antigens in mice. Truncation of these peptides revealed that NY-ESO-1-specific CD8(+) T cells recognized D(d)-restricted 8mer peptides, NY-ESO-181-88. MAGE-A4
In developed countries, colorectal cancer (CRC) is a leading cause of cancer. Because this disease develops slowly over years and often starts with the apparition of polyps that may evolve in a malignant tumor, this cancer is particularly suitable for screening. However, current techniques of detection lack specificity and sensitivity, or are invasive, reducing the compliance of the patients. Thus, there is a need to find new biomarkers to improve the detection of CRC at an early stage and to reduce its incidence. In this work, we focused on autoantibodies (aAb) produced by the immune system as potential CRC biomarkers since they combine several advantages including stability, specificity and early production in the course of the disease. Human tumor-associated antigens (TAA) of interest were identified by the serological proteome analysis (SERPA) approach, based on the combination of 2D-gel electrophoresis and after transfer onto membranes, immunoblotting with sera from tumor-bearing mice or ...
Cancer testis (CT) antigens are promising targets for cancer immunotherapies such as cancer vaccines and genetically modified adoptive T cell therapy. In this study, we evaluated the expression of three CT antigens, melanoma-associated antigen A4 (MAGE-A4), New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) and sarcoma antigen gene (SAGE). MAGE-A4, NY-ESO-1 and/or SAGE antigen expression in tumour samples was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Informed consent was obtained from individuals prior to study enrolment. In total, 585 samples in 21 tumour types were evaluated between June 2009 and March 2018. The positive expression rates of these CT antigens were as follows: MAGE-A4, 34.6% (range, 30.7-38.7); NY-ESO-1, 21.0% (range, 17.2-25.1); and SAGE, 21.8% (range, 18.5-25.4). The MAGE-A4 antigen was expressed in 54.9% of oesophageal cancers, 37.5% of head and neck cancers, 35.0% of gastric cancers and 34.2% of ovarian cancers; the NY-ESO-1 antigen was
Sperm protein (Sp17) is an attractive target for ovarian cancer (OC) vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17) was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and ...
The first tumor-specific shared antigens and the cancer-germline genes that code for these antigens were identified with antitumor cytolytic T lymphocytes obtained from cancer patients. A few HLA class I-restricted antigenic peptides were identified by this direct approach. A large set of additional cancer-germline genes have now been identified by purely genetic approaches or by screening tumor cDNA expression libraries with the serum of cancer patients. As a result, a vast number of sequences are known that can code for tumor-specific shared antigens, but most of the encoded antigenic peptides have not yet been identified. We review here recent reverse immunology approaches for the identification of new antigenic peptides. They are based on in vitro stimulation of naive T cells with dendritic cells that have either been loaded with a cancer-germline protein or that have been transduced with viruses carrying cancer-germline coding sequences. These approaches have led to the identification of many
A number of human tumor antigens have been characterized recently using cytolytic T lymphocytes (CTL) as screening tools. Some of them are encoded by MAGE-type genes, which are silent in normal tissues except in male germ cells, but are activated in a variety of tumors. These tumor-specific shared antigens appear to be promising targets for cancer immunotherapy. However, the choice of these antigens as targets has been questioned because of the lack of direct evidence that in vivo responses against such antigens can lead to tumor rejection. The antigen encoded by the mouse gene P1A represents the only available animal model system for MAGE-type tumor antigens. We show here that mice immunized by injection of L1210 leukemia cells expressing P1A and B7-1 (L1210.P1A.B7-1) are efficiently protected against a challenge with a lethal dose of mastocytoma P815 tumor cells, which express P1A. Mice immunized with L1210 cells expressing B7-1 but not P1A were not protected. Furthermore, we observed that P1A
Using the TCGA data set for malignant melanoma, the patients were segregated according to the presence or absence of the T cell-inflamed gene expression signature in the tumor microenvironment. Transcriptional profiling revealed no differences in the levels of cancer-testis (CT) antigens or differentiation antigens between the hot and the cold tumors. Using exome sequencing of tumor versus germline, a range of 18 to 3001 of non-synonymous mutations was observed in both cohorts. Using the syfpeithi algorithm for HLA-A*0201 patients, a median of 123 mutations having a high immunogenicity score were found in the T cell-inflamed cohort versus 176 in the non-T cell-inflamed. To confirm actual immunogenicity, 321 peptides from hot tumors and 409 peptides from cold tumors have been synthesized. Using a high-throughput T2 binding assay, peptides from both cohorts were found to bind to HLA-A*0201. In vitro priming of T cells using autologous dendritic cells also revealed that peptides from both cohorts ...
Abstract Background The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA). Methods To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. ...
Mass spectrometry helps identify antigens on tumor cells - posted in Immunology Products: Using an analytical technique called mass spectrometry (MS) that helps identify the chemical constitution of a substance, Angela M. Krackhardt and colleagues from Technische Universitat Munchen and collaborators identify novel target antigens for cancer intervention. Michal Bassani-Sternberg from Max Planck Institute of Biochemistry is the first author. CusAb offers protein. Immunotherapy works...
Alt. Names/Synonyms: ACSTD1; Adenocarcinoma-associated antigen; carcinoma-associated antigen GA733-2; Cell surface glycoprotein Trop-1; CO-17A; CO17-1A; DIAR5; EGP; EGP-2; EGP314; EGP34; EGP40; Ep-CAM; EPCAM; Epithelial cell adhesion molecule; Epithelial cell surface antigen; Epithelial glycoprotein; Epithelial glycoprotein 314; ESA; GA733-2; hEGP-2; hEGP314; HNPCC8; human epithelial glycoprotein-2; KS 1/4 antigen; KS1/4; KSA; M1S2; M4S1; Major gastrointestinal tumor-associated protein GA733-2; membrane component, chromosome 4, surface marker (35kD glycoprotein); MIC18; MK-1; TACST-1; TACSTD1; TROP1; Tumor-associated calcium signal transducer 1 ...
Cancer treatment vaccines are designed to treat cancers that have already developed rather than to prevent them in the first place. Cancer treatment vaccines contain cancer-associated antigens to enhance the immune systems response to a patients tumor cells. The cancer-associated antigens can be proteins or another type of molecule found on the surface of or inside cancer cells that can stimulate B cells or killer T cells to attack them.. Some vaccines that are under development target antigens that are found on or in many types of cancer cells. These types of cancer vaccines are being tested in clinical trials in patients with a variety of cancers, including prostate, colorectal, lung, breast, and thyroid cancers. Other cancer vaccines target antigens that are unique to a specific cancer type (7-14). Still other vaccines are designed against an antigen specific to one patients tumor and need to be customized for each patient. The one cancer treatment vaccine that has received FDA approval, ...
PURPOSE: NY-ESO-1, one of the most immunogenic tumor antigens, is expressed in 15% to 25% of metastatic prostate cancers. The immunological and clinical effects of vaccination with recombinant NY-ESO-1 protein combined with CpG as adjuvant were evaluated. EXPERIMENTAL DESIGN: In a phase I clinical study, patients with advanced prostate cancer were vaccinated with recombinant NY-ESO-1 protein (100 μg) mixed with CpG 7909 (2.5 mg) every 3 weeks intradermally for 4 doses. Objectives of the study were the safety of the vaccine and changes of specific humoral and cellular immunological responses to NY-ESO-1 in relation to detectable NY-ESO-1 expression in the individual tumor. RESULTS: All 12 baseline sero-negative patients developed high-titer NY-ESO-1 antibody responses. B-cell epitope mapping identified NY-ESO-1 p91-110 to be recognized most frequently by vaccine-induced antibodies. Two patients developed significant antibody titers against the adjuvant CpG. NY-ESO-1-specific CD4+ and/or CD8+ ...
Cancer-Testis Antigens: -Smart- Biomarkers for Diagnosis and Prognosis of Prostate and Other Cancers. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The isolation of CD8+ cytolytic T cells (CTL) reactive to the autologous tumors in cancer patients has allowed, during the last decade, the identification of several categories of tumor-associated antigens that can be the target of tumor-specific immune responses. Among them, one of the most relevant for the development of cancer vaccines is the group of the so-called Cancer-Testis (CT) antigens, which are expressed by tumor cells but not by most somatic adult tissues, with the exception of testis. Because of their expression commonly found in tumors of various histological types, CT antigen-derived peptides recognized by tumor reactive CTL are relevant candidates for generic vaccination of cancer patients.. In the last two years, we have analyzed the natural response to four CT antigen-derived HLA-A2 restricted epitopes recognized by tumor reactive CTL. Three of them correspond to the previously described peptides from MAGE-A10 (254-262), NY-ESO-1 (157-165) and CAMEL (1-11). The fourth peptide ...
This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008 ...
In this issue of Clinical Cancer Research, a new development in adoptive T-cell therapy experimental mouse tumor model is reported by Leisegang and colleagues (1).. In retrospect, the 1990s were considered a golden period for tumor immunology when many tumor antigens recognized by T cells were identified. The antigens reported by Boon and colleagues in both murine and human cancers (2, 3) were derived from genes that are overexpressed in cancer and fetal tissues (4). The second class of unmutated antigens recognized by tumor-reactive T cells is tissue-specific antigens that are also found in tumor cells (5). These unmutated tumor antigens were favored for cancer vaccines and cancer therapy because they are present in a high proportion of human cancers. However, the classical study by Prehn and Main (6) has cast a long shadow on the utility of the shared tumor antigen, as their in vivo analysis showed that tumor rejection antigens are by and large individually specific. In supporting this notion, ...
Principal Investigator:ARAKI Nobuhito, Project Period (FY):1995 - 1997, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Orthopaedic surgery
Three of nine patients (33%) remain in complete clinical remission at 25, 38, and 52 months, respectively. The cancer-testis antigen NY-ESO-1 is expressed in greater than 40% of advanced epithelial ovarian cancers and represents a promising immunotherapeutic target. In a small Phase I (safety and immunogenicity) clinical trial conducted by Memorial Sloan-Kettering Cancer Center and…
There is clear evidence that tumor patients are able to generate TAA-specific T cell immunity spontaneously. Whereas the presence of tumor-specific T cells has been shown by many groups and for various tumor types, much less is known about the function of TAA-specific T cells in vivo. Most of the TAAs including differentiation, germ-line, and shared overexpressed antigens are not tumor specific but are also expressed at low levels in certain nonmalignant tissues. This should influence the type of T cell response because deletion of functional high-avidity self-reactive T cells in the thymus as well as peripheral deletion or anergy was shown in various animal models (reviewed in Ref. 74 ). There are a few recent studies analyzing the functional avidity of TAA-specific T cells in patients. In leukemia patients, low-avidity T cells to proteinase 3, which are able to kill leukemia cells, can readily be expanded. However, high-avidity T cells can also be expanded from patients in cytogenetic ...
Adoptive transfer of T cell receptor-engineered (TCR-engineered) T cells is a promising approach in cancer therapy but needs improvement for more effective treatment of solid tumors. While most clinical approaches have focused on CD8+ T cells, the importance of CD4+ T cells in mediating tumor regression has become apparent. Regarding shared (self) tumor antigens, it is unclear whether the human CD4+ T cell repertoire has been shaped by tolerance mechanisms and lacks highly functional TCRs suitable for therapy. Here, TCRs against the tumor-associated antigen NY-ESO-1 were isolated either from human CD4+ T cells or from mice that express a diverse human TCR repertoire with HLA-DRA/DRB1*0401 restriction and are NY-ESO-1 negative. NY-ESO-1-reactive TCRs from the mice showed superior recognition of tumor cells and higher functional activity compared with TCRs from humans. We identified a candidate TCR, TCR-3598_2, which was expressed in CD4+ T cells and caused tumor regression in combination with ...
Adoptive transfer of T cell receptor-engineered (TCR-engineered) T cells is a promising approach in cancer therapy but needs improvement for more effective treatment of solid tumors. While most clinical approaches have focused on CD8+ T cells, the importance of CD4+ T cells in mediating tumor regression has become apparent. Regarding shared (self) tumor antigens, it is unclear whether the human CD4+ T cell repertoire has been shaped by tolerance mechanisms and lacks highly functional TCRs suitable for therapy. Here, TCRs against the tumor-associated antigen NY-ESO-1 were isolated either from human CD4+ T cells or from mice that express a diverse human TCR repertoire with HLA-DRA/DRB1*0401 restriction and are NY-ESO-1 negative. NY-ESO-1-reactive TCRs from the mice showed superior recognition of tumor cells and higher functional activity compared with TCRs from humans. We identified a candidate TCR, TCR-3598_2, which was expressed in CD4+ T cells and caused tumor regression in combination with ...
Adoptive transfer of T cell receptor-engineered (TCR-engineered) T cells is a promising approach in cancer therapy but needs improvement for more effective treatment of solid tumors. While most clinical approaches have focused on CD8+ T cells, the importance of CD4+ T cells in mediating tumor regression has become apparent. Regarding shared (self) tumor antigens, it is unclear whether the human CD4+ T cell repertoire has been shaped by tolerance mechanisms and lacks highly functional TCRs suitable for therapy. Here, TCRs against the tumor-associated antigen NY-ESO-1 were isolated either from human CD4+ T cells or from mice that express a diverse human TCR repertoire with HLA-DRA/DRB1*0401 restriction and are NY-ESO-1 negative. NY-ESO-1-reactive TCRs from the mice showed superior recognition of tumor cells and higher functional activity compared with TCRs from humans. We identified a candidate TCR, TCR-3598_2, which was expressed in CD4+ T cells and caused tumor regression in combination with ...
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Background: This study aimed to assess the prognostic value of receptor binding cancer antigen expressed on SiSo cells (RCAS1) expression and host immune response in gastric carcinomas. Methods: We i
ASN004 is an Antibody Drug Conjugate (ADC) that targets the 5T4 oncofetal antigen (trophoblast glycoprotein), which is highly expressed in a wide range of malignant tumors, while having very limited expression in normal tissues. ASN004 incorporates a novel single-chain homo-dimer antibody, Fleximer® linker technology (Mersana Therapeutics), and several cytotoxic dolastatin (auristatin) analog warheads per ADC molecule (drug/antibody ratio ∼15). ASN004 shows high affinity for the 5T4 antigen and for 5T4-expressing tumor cells. As well, ASN004 shows potent cytotoxicity that is selective for 5T4-expressing tumor cells. ASN004 provides strong tumor regression and tumor-free survivors in multiple tumor xenograft models, at well-tolerated doses as low as 0.3 mg/kg iv. Furthermore, ASN004 causes tumor regression when administered to xenografts bearing more advanced (500 mm3) tumors. Robust, potent efficacy for ASN004 has also been demonstrated in head-to-head comparison studies with relevant ...
As mentioned earlier, another aspect of cancer is a failure of the immune system to recognize tumor specific antigens. Cytokines behave similarly to growth factors, causing cells to grow and divide; however, they are the predominant cellular signals of the immune system and have other actions such as attaching (chemotaxis) white blood cells to the site of an infection. Interestingly, it has been shown cancer cells signal suppressor T cells to protect them from killer T cells against unique tumor antigens. The mechanism of recruitment is not fully understood but TGF-b and interleukin 10 (IL-10) have been implicated in regulatory T cell function. While some cytokines play a role in suppressing the immune system, others such as IL-2 play a role in activating the immune system. One of the strategies in battling cancer has been to exploit the ability of interleukin-2 (IL-2) to heighten the immune response. IL-2 has been shown to cause complete remission in 6% of patients with renal cancer ...
We have shown that both regressor and progressor clones can be isolated from a UV regressor tumor, RD-1024. Although the daughter clones are characterized by differences in tumorigenic potential in normal transplant hosts, they nevertheless seem to express the same major tumor rejection antigens, because immunization with either the regressor parent tumor, RD-1024, or with regressor Cl 8 protects against subsequent challenge with progressor C1 4 or Cl 9. Consistent with the in vivo-generated data is the evidence that draining lymph node cells with functional specificity for regressor Cl 8 are capable of cross-reactive cytotoxicity in an in vitro chromium release assay. We have demonstrated an indirect interaction occurring in vivo between regressor and progressor cells, in that Cl 8 cells have the ability to influence the outcome of simultaneous or sequential challenge with Cl 4 or Cl 9 cells. Because 500 rad of gamma irradiation has been shown to compromise the ability of mice to respond to a ...
In 2001, we have started compiling what we thought were the most relevant human tumor antigens, and created a database. Each line corresponds to a peptide, considered to be a tumor antigen given that it is recognized by T lymphocytes that also recognize tumor cells expressing the parent protein.
Objective(s): Multi-epitopic protein vaccines and direction of vaccine delivery to dendritic cells (DCs) are encouraging approaches for enhancing immune system reactions against mutable pathogens. The very best cultivation condition for creation of HIVtop4 proteins can be induction by 1 mM IPTG during 4 hr in 2XYT moderate. The final focus of purified proteins was 500 g/ml. genome offers led to Vandetanib the introduction of vaccines incorporating just these essential epitopes to be able to elicit the mandatory immunologic response (5, 6). These epitope centered vaccines possess potential benefits like as biosafety, exact control over Vandetanib the disease fighting capability activation and capability of concentrate on conserved and extremely immunogenic antigen areas (7). Among the HIV-1 antigens, Gag, Tat, Env and Pol have obtained substantial interest because of the essential tasks in viral existence routine (8, 9), and also have sites in the viral genome mapping to both T helper and T ...
Cytolytic CD8 T cells fall into two subpopulations based on cytokine-secretion. Type 1 CD8 cells Tc1 characteristically secrete IFN-gamma, whereas type 2 CD8 cells Tc2 secrete ILA and IL- 5. Using a TSA mammary carcinoma cell line, expressing HA as a surrogate tumor-associated antigen, we assessed the therapeutic effects of adoptively transferred HA tumor-specific Tc1 and Tc2 effector cells in mice with established malignancy. Both Tc1 and Tc2 subpopulations effectively delayed tumor cell growth and mediated tumor regression in mice with established malignancy. Flow cytometric analysis showed that donor cells accumulated at the tumor site and antitumor effects were highly tumor specific. First-line treatment with either methotrexate MTX or 5-Fluorouracil 5-FU chemotherapeutic agents markedly enhanced the co- therapeutic effects of Tc2 effector cells. Whereas, MTX but not 5-FU, acted synergistically with corresponding Tc1 immunotherapy. Although effector cell therapies in combination with chemotherapy
PRP31_HUMAN RecName: Full=U4/U6 small nuclear ribonucleoprotein Prp31; AltName: Full=Pre-mRNA-processing factor 31; AltName: Full=Serologically defined breast cancer antigen NY-BR-99; AltName: Full=U4/U6 snRNP 61 kDa protein; Short=Protein 61K; Short=hPrp31 ...
Tikcro Technologies Ltd., powered by a novel 3D antigen design technology, generates new ‎antibodies that block receptor/ligand surface domains of immune modulators and re-‎activate the bodys immune system to fight cancer. Our antibodies are in various pre-‎clinical stages.. Following extensive collaborative research with the Weizmann Institute of Science in ‎Israel, we are developing drug-candidates by leveraging a unique antigen design ‎technology for the generation of new functional blocking antibodies. This approach has ‎shown early success with pipeline below. Going forward, in 2017-2018 we plan to advance ‎with early-stage candidates to rigorous pre-clinical trials and aim to build sufficient data for ‎further progress and clinical trials.‎. ...
Janelle, Valérie; Lamarre, Alain (2014). How Informative is the Immune Response Against Surrogate Tumor Antigens to Assess Antitumor Immunity? Frontiers in oncology , vol. 4 , nº 135. p. 1-3. DOI: 10.3389/fonc.2014.00135. ...
TROP2 belongs to the TACSTD family and is a cell surface glycoprotein encoded by the TACSTD2 gene. It is also known as tumor-associated calcium signal transducer 2 (TACSTD2), epidermal glycoprotein 1 (EGP-1), and gastrointestinal tumor-associated antigen (GA733-1) and surface mar
Alternative Name: ADAM Metallopeptidase Domain 2, Fertilin β, Cancer/Testis Antigen 15, Disintegrin And Metalloproteinase Domain-Containing Protein 2, PH30-Beta, FTNB, CT15, PH30, EC 3.4.24, PH-30b, CRYN1, CRYN2, PH-30 ...
Zdroj: Immunol Lett. 2020 Mar;219:46-53. doi: 10.1016/j.imlet.2020.01.001. Epub 2020 Jan 10. Authors: O. Palata, N. Podzimkova Hradilova, D. Mysiková, B. Kutna, H. Mrazkova, R. Lischke, R. Spisek, I. Adkins. ...
Squamous cell carcinoma antigen: a role in the early identification of nodal metastases in men with squamous cell carcinoma of the penis. To evaluate whether serum squamous cell carcinoma antigen (SCCAg) measurements may be of use in identifying nodal metastases in patients with SCC of the penis after treating the primary tumour. The levels of SCCAg were analysed in 11 men with penile SCC between 1994 and 2001. An elevated SCCAg level had a sensitivity of 57% (95% confidence interval, CI, 18-90%) and a specificity of 100% (CI 40-100%) for nodal metastases. Levels of SCCAg increased exponentially in patients who developed nodal metastases after treatment of the primary tumour, and were elevated before clinical or radiological evidence of nodal disease. Either the absolute level or the rate of rise of SCCAg may be a useful tool with which to follow patients after excision of the primary tumour. It may be more sensitive than computed tomography and magnetic resonanc imaging in detecting recurrence, ...
Our analysis of cervical cancer patients treated with CCRT indicated that the sensitivity and specificity of two consecutive increases in serum SCC-Ag for predicting tumor recurrence were 61.1% and 97.9%, respectively. These results are comparable to previously reported results. For example, several studies of cervical cancer patients showed that an elevated serum SCC-Ag level was associated with 70-92% rate of recurrent tumors [8, 11, 14-19]; in addition, the specificity of SCC-Ag during the follow-up period was quite high, varying from 95 to 98% [7, 16, 20]. According to our ROC analysis, the area under the ROC curve indicated the ΔSCC-Ag was 0.83 for patients who had elevated pre-treatment SCC-Ag. Therefore, our results indicate that ΔSCC-Ag had good clinical performance in detection of recurrent disease.. As described above, we defined biochemical failure as two consecutive SCC-Ag values above normal. There are no standard criteria used to define biochemical failure in cervical cancer, and ...
TY - JOUR. T1 - Carbonic anhydrase IX expression in renal neoplasms. T2 - Correlation with tumor type and grade. AU - Genega, Elizabeth M.. AU - Ghebremichael, Musie. AU - Najarian, Robert. AU - Fu, Yineng. AU - Wang, Yihong. AU - Argani, Pedram. AU - Grisanzio, Chiara. AU - Signoretti, Sabina. PY - 2010/12. Y1 - 2010/12. N2 - Carbonic anhydrase IX (CAIX), a hypoxia-induced protein, is expressed in some renal tumors. We evaluated its immunohistochemical expression in 317 primary and 42 metastatic renal neoplasms (186 clear cell, 52 papillary, 35 chromophobe, 47 unclassified, and 15 Xp11.2 translocation renal cell carcinomas [RCCs]; 26 oncocytomas; 2 metanephric adenomas; 1 urothelial carcinoma; 1 mixed epithelial and stromal tumor; and 1 angiomyolipoma); 7 neoplasms were unknown as to whether they were primary or metastatic. We also correlated expression with tumor type and grade. Variable staining was seen in clear cell, papillary, unclassified, and Xp11.2 translocation carcinomas. One ...
PURPOSE: To evaluate carbonic anhydrase (CA) IX as a surrogate marker of hypoxia and investigate the prognostic significance of different patterns of expression in non-small-cell lung cancer (NSCLC). METHODS: Standard immunohistochemical techniques were used to study CA IX expression in 175 resected NSCLC tumors. CA IX expression was determined by Western blotting in A549 cell lines grown under normoxic and hypoxic conditions. Measurements from microvessels to CA IX positivity were obtained. RESULTS: CA IX immunostaining was detected in 81.8% of patients. Membranous (m) (P =.005), cytoplasmic (c) (P =.018), and stromal (P |.001) CA IX expression correlated with the extent of tumor necrosis (TN). The mean distance from vascular endothelium to the start of tumor cell positivity was 90 micro m, which equates to an oxygen pressure of 5.77 mmHg. The distance to blood vessels from individual tumor cells or tumor cell clusters was greater if they expressed mCA IX than if they did not (P |.001). Hypoxic
TY - JOUR. T1 - Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12. AU - Mortarini, Roberta. AU - Borri, Alessandra. AU - Tragni, Gabrina. AU - Bersani, Ilaria. AU - Vegetti, Claudia. AU - Bajetta, Emilio. AU - Pilotti, Silvana. AU - Cerundolo, Vincenzo. AU - Anichini, Andrea. PY - 2000/7/1. Y1 - 2000/7/1. N2 - Systemic effects on T-cell-mediated antitumor immunity, on expression of T-cell adhesion/homing receptors, and on the promotion of T-cell infiltration of neoplastic tissue may represent key steps for the efficacy of immunological therapies of cancer. In this study, we investigated whether these processes can be promoted by s.c. administration of low-dose (0.5 μg/kg) recombinant human interleukin-12 (rHuIL-12) to metastatic melanoma patients. A striking burst of HLA-restricted CTL precursors (CTLp) directed to autologous tumor was documented in peripheral blood by a ...
The protein encoded by this gene is an RNA-binding nuclear protein that is a tumor-rejection antigen. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. This gene product is found to be an important cellular factor for HIV-1 gene expression and viral replication. It also associates transiently with U6 and U4/U6 snRNPs during the recycling phase of the spliceosome cycle. This encoded protein is thought to be involved in the regulation of mRNA splicing. [provided by RefSeq, Jul 2008 ...
TY - JOUR. T1 - Surface Marker Epithelial Cell Adhesion Molecule and E-cadherin Facilitate the Identification and Selection of Induced Pluripotent Stem Cells. AU - Chen, Hsin Fu. AU - Chuang, Ching Yu. AU - Lee, Wen Chih. AU - Huang, Hsiang Po. AU - Wu, Han Chung. AU - Ho, Hong Nerng. AU - Chen, Yu Ju. AU - Kuo, Hung Chih. PY - 2011/9/1. Y1 - 2011/9/1. N2 - The derivation of induced pluripotent stem cells (iPSCs) requires not only efficient reprogramming methods, but also reliable markers for identification and purification of iPSCs. Here, we demonstrate that surface markers, epithelial cells adhesion molecule (EpCAM) and epithelial cadherin (E-cadherin) can be used for efficient identification and/or isolation of reprogrammed mouse iPSCs. By viral transduction of Oct4, Sox2, Klf4 and n- or c-Myc into mouse embryonic fibroblasts, we observed that the conventional mouse embryonic stem cell (mESC) markers, alkaline phosphatase (AP) and stage-specific embryonic antigen 1 (SSEA1), were expressed in ...
Buy Psca recombinant protein, Prostate stem cell antigen Recombinant Protein-P57096.1 (MBS962351) product datasheet at MyBioSource, Recombinant Proteins
Prostate stem cell antigen expression is associated with gleason score, seminal vesicle invasion and capsular invasion in prostate cancer.: We found that high P
Human being epithelial cell adhesion molecule (HEPCAM) is a tumor-associated antigen frequently expressed in carcinomas, which promotes proliferation after controlled intramembrane proteolysis. which can be connected with mutations from the gene (9). Although Lei (8) reported a particular amount of embryonic lethality, the nice known reasons for these obvious discrepancies in phenotypes stay unknown. Furthermore, molecular systems in charge of the noticed Bay 11-7821 congenital tufting enteropathy phenotypes had been deviating. Guerra (7) suggested a job for adherens junctions having a mislocalization of E-cadherin and -catenin in the developing intestine (7), whereas Lei (8) excluded the participation of E-cadherin and -catenin, which were located properly, and a function was stated by them for mEpcam in the recruitment Bay 11-7821 of claudins to tight junctions. A job for Epcam in the forming of practical adherens junctions via E-cadherin was further referred to during epiboly Rabbit ...
Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors but not in any normal adult tissues except germ cells and occasionally placenta. Because of this tumor-associated pattern of expression, CTAs are regarded as potential vaccine targets. The expression of CTAs in gastrointestinal stromal tumors (GIST) has not been analyzed systematically previously. The present study was performed to analyze the expression of CTA in GIST and to determine if CTA expression correlates with prognosis. Thirty-five GIST patients were retrospectively analyzed for their expression of CTAs by immunohistochemistry using the following monoclonal antibodies (mAb/antigen): MA454/MAGE-A1, M3H67/MAGE-A3, 57B/MAGE-A4, CT7-33/MAGE-C1 and E978/NY-ESO-1. Fourteen tumors (40%) expressed 1 or more of the 5 CTAs tested. Fourteen percent (n = 5/35) were positive for MAGE-A1, MAGE-A3 or MAGE-A4, respectively. Twenty-six percent (n = 9/35) stained positive for MAGE-C1 and 20% (n = 7/35) for NY-ESO-1. A
As a leading supplier of innovative life science research tools, Creative Diagnostics continues to expand its products portfolio by offering of unique antigens for researchers globally, which is supported by extensive research, development, and validation for superior quality. The addition of antigen products and services will enable scientists to work on more specific projects, and also provide leading researchers and diagnostic manufacturers with a more diverse antigen selection, which facilitates the development of assays with greater specificity and sensitivity.. These newly released antigens are rigorously tested to meet the demand in research and development and are featured with excellent quality, including Viral Antigens, Bacterial Antigens, Fungal Antigens, Parasitic Antigens, Immunoglobulin, Hapten, Cardiac Biomarkers and so on. With this expanded offering of antigens products, Creative Diagnostics enables scientists to achieve more complete analysis experiments. These products along ...
Background: The delivery of specific immunotherapies for malignant tumours requires the identification of relevant tumour antigens and sequences from these which can be used to stimulate protective T cell-mediated immunity. HAGE (DDX43) is a cancer testis antigen belonging to the DEAD box family of helicases found by our group to be over-expressed in many solid cancers including breast cancer (Mathieu et al.1) immunogenic (Mathieu et al.2 and to be a biomarker for poor prognosis as well as a predictor of chemotherapy response in breast cancer (Abdel-fatah et al.3). We propose that HAGE might be a novel immunotherapeutic target for patients bearing breast cancers expressing this antigen. The aim of this study is to identify strongly immunogenic HAGE-derived sequences which can be used for the development of a therapeutic vaccine for HAGE positive cancer.. Experimental Design: The HAGE-derived sequences were identified and assessed after: (i) using a computer-based epitope predictive tool; (ii) ...
Human melanoma antigen (MAGE) genes have been shown to be expressed in both normal tissues and in various tumors and tumor related cells. Two types of MAGE genes have been characterized based on their expression: type-I members are silent in all normal tissues except for in the male germ line and placenta while type-II members are expressed ubiquitously in both tumor and normal cells (Figure 1). MAGE-C subfamily members are type-I genes expressed in various tumor types; their proteins are tumor-specific antigens that can be recognized by cytolytic T lymphocytes. MAGE-D subfamily members are type-II members they do not encode for those tumor-specific antigens seen in type-I MAGE and are also expressed ubiquitously in normal adult tissues. While MAGE genes could be targets for immunotherapy, information on the function and expression pattern of MAGE-C and MAGE D genes, however, remains incomplete. Analysis of the gene expression of type-I and type-II MAGE genes in various histological tumors may ...
Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell-cell adhesion in epithelia. EpCAM is also involved in cell signaling, migration, proliferation, and differentiation. Additionally, EpCAM has oncogenic potential via its capacity to upregulate c-myc, e-fabp, and cyclins A & E. Since EpCAM is expressed exclusively in epithelia and epithelial-derived neoplasms, EpCAM can be used as diagnostic marker for various cancers. It appears to play a role in tumorigenesis and metastasis of carcinomas, so it can also act as a potential prognostic marker and as a potential target for immunotherapeutic strategies. First discovered in 1979, EpCAM was initially described as a dominant surface antigen on human colon carcinoma. Because of its prevalence on many carcinomas, it has been discovered many different times. EpCAM therefore has many aliases the most notable of which include TACSTD1 (tumor-associated calcium signal transducer 1), CD326 ...
A discovery by scientists working with the Health Sciences Initiative could lead the way to a vaccine against prostate cancer. The researchers, led by immunologist James Allison, a Howard Hughes Medical Institute investigator and professor of molecular and cell biology, found a protein on prostate cancer cells that tips off the immune system to the tumor s presence and brings in an armada of immune cells to destroy it.. If the protein, called an antigen, is truly unique to prostate cancer cells, it could lead to diagnostics for prostate cancer and a potential vaccine therapy against the disease, which is the second leading cause of cancer death in men, after lung cancer. This is the first prostate cancer antigen found.. The hope is twofold, Allison said. One, knowing what the specific target of the immune system is, we can do some very direct studies of whether it is a prognosticator of favorable outcome of disease. And two, we can start thinking about using the antigens to develop a specific ...
The human pancarcinoma-associated epithelial cell adhesion molecule (EpCAM) (EGP-2, CO17-1A) is a well-known target for carcinoma-directed immunotherapy. Mouse-derived mAbs directed to EpCAM have been used to treat colon carcinoma patients showing well-tolerable toxic side effects but limited antitu …
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Because tumor-specific cytotoxic T lymphocytes (CTL) recognize tumor antigen associated with MHC class I molecules expressed on the tumor surface, any alteration in the tumor antigen processing and presentation will greatly affect CTL immunity. In fact, downregulation or complete loss of MHC I molecules have been demonstrated in a wide array of tumors, particularly prostate, colon, lung, and breast cancers (5-12). Disruption or downregulation of antigen processing components, such as TAP (transporters associated with antigen processing) and LMP (components of the proteasome complex) genes have also been observed in several tumor types, including breast, prostate, and renal cancers (13-15). Another tactic tumors exploit is downregulation or alteration of tumor antigens. Several independent research groups described the loss of melanoma-associated antigen either during treatment by adoptive transfer of ex vivo expanded antigen-specific CTL (16) or during immune therapy by tumor vaccinations ...
Recombinant Human Epithelial cell adhesion molecule(EPCAM),partial von Cusabio bei SZABO-SCANDIC erhältlich. Weiteres zu Proteine & Peptide finden Sie hier.
Recombinant Human Epithelial cell adhesion molecule(EPCAM),partial von Cusabio bei SZABO-SCANDIC erhältlich. Weiteres zu Proteine & Peptide finden Sie hier.
NY-ESO-1 is a human tumor antigen of the cancer/testis family. It is highly expressed in many poor-prognosis melanomas. It is being studied as possible target for a cancer vaccine or immunotherapy. It is a target for some experimental engineered T-cell therapies for myeloma. Lloyd J. Old#Major Discoveries Gnjatic, S; et al. (2006). NY-ESO-1: review of an immunogenic tumor antigen. Advances in Cancer Research. 95: 1-30. doi:10.1016/S0065-230X(06)95001-5. PMID 16860654. van Rhee, F (15 May 2005). NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses (PDF). Blood. 105 (10): 3939-3944. doi:10.1182/blood-2004-09-3707. PMC 1895070 . PMID 15671442. Rapoport, AP; et al. (20 July 2015). NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nature Medicine. 21 (8): 914-921. doi:10.1038/nm.3910. PMC 4529359 . PMID 26193344. A novel human-derived antibody against NY-ESO-1 ...
Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression of ALDH1 and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen, CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude
0192] Numerous tumor antigens are known in the art, including: (a) cancer-testis antigens such as NY-ESO-1, SSX2, SCP1 as well as RAGE, BAGE, GAGE and MAGE family polypeptides, for example, GAGE-1, GAGE-2, MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-5, MAGE-6, and MAGE-12 (which can be used, for example, to address melanoma, lung, head and neck, NSCLC, breast, gastrointestinal, and bladder tumors), (b) mutated antigens, for example, p53 (associated with various solid tumors, e.g., colorectal, lung, head and neck cancer), p21/Ras (associated with, e.g., melanoma, pancreatic cancer and colorectal cancer), CDK4 (associated with, e.g., melanoma), MUM1 (associated with, e.g., melanoma), caspase-8 (associated with, e.g., head and neck cancer), CIA 0205 (associated with, e.g., bladder cancer), HLA-A2-R1701, beta catenin (associated with, e.g., melanoma), TCR (associated with, e.g., T-cell non-Hodgkins lymphoma), BCR-abl (associated with, e.g., chronic myelogenous leukemia), triosephosphate isomerase, KIA ...
Treatment with the demethylating agent 5-Azacytidine leads to prolonged survival for patients with myelodysplastic syndrome, and the demethylation induces upregulation of cancer-testis antigens. Cancer-testis antigens are well-known targets for immune recognition in cancer, and the immune system may have a role in this treatment regimen. We show here that 5-Azacytidine treatment leads to increased T-cell recognition of tumor cells. T-cell responses against a large panel of cancer-testis antigens were detected before treatment, and these responses were further induced upon initiation of treatment. These characteristics point to an ideal combination of 5-Azacytidine and immune therapy to preferentially boost T-cell responses against cancer-testis antigens. To initiate such combination therapy, essential knowledge is required about the general immune modulatory effect of 5-Azacytidine. We therefore examined potential treatment effects on both immune stimulatory (CD8 and CD4 T cells and Natural ...
Gastric cancers are responsible for the second most cancer-related deaths worldwide. Although medical and surgical treatments have improved for gastric cancers, survival rates remain poor for both lung and gastric cancer patients.. Currently, approaches for immunotherapy in gastric cancer rely on the use of immunocytes, white blood cells that produce antibodies or trigger an immune response. Specifically, the current immunotherapy is designed to activate tumor specific cytotoxic T cells or to specifically bind target molecules or proteins expressed on the malignant tumor cells. In their research, a number of tumor rejection antigens have also been identified.. Experimental vaccination strategies are also in trial, including use of whole protein and peptide vaccines based on identification of peptides recognized by cytotoxic T lymphocytes and helper T lymphocytes. Tumor rejection antigens are selectively expressed in human tumors including gastric cancer, which can be recognized by cytotoxic T ...
TY - JOUR. T1 - MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. AU - Yang, Bing. AU - OHerrin, Sean M.. AU - Wu, Jianqiang. AU - Reagan-Shaw, Shannon. AU - Ma, Yongsheng. AU - Bhat, Kumar M.R.. AU - Gravekamp, Claudia. AU - Setaluri, Vijayasaradhi. AU - Peters, Noel. AU - Hoffmann, F. Michael. AU - Peng, Hongzhuang. AU - Ivanov, Alexey V.. AU - Simpson, Andrew J.G.. AU - Longley, B. Jack. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2007/10/15. Y1 - 2007/10/15. N2 - The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. ...
Human B melanoma antigen ELISA Kit;Human antigen MZ2-BA ELISA Kit;Human cancer/testis antigen 2.1 ELISA Kit;Human CT2.1 ELISA Kit;Human BAGE1 ELISA Kit;Human B melanoma antigen 1 ELISA Kit;Human cancer/testis antigen family 2, member 1 ELISA Kit ...
Vaccines that prevent disease have profoundly changed the lives of billions of people around the world, says Matthew M. Davis, M.D., MAPP, associate professor of pediatrics and internal medicine at the University of Michigan Medical School. A national strategy for therapeutic cancer vaccines would help emphasize development and regulatory approval for vaccines targeting cancers that currently do not have other good therapeutic options ...
Much has been learned in recent years concerning the nature of tumor antigens recognized by T cells. To apply this knowledge clinically, the nature of the host response to individual and multiple tumor antigens has to be characterized. This will help to define the efficacy of immune surveillance and the immune status of the host following exposure to tumor antigens expressed on pre-neoplastic tissue. To approach these questions, we have developed a transgenic mouse which expresses the tumor-specific antigen P91A. The single amino acid substitution in P91A results in the expression of a new MHC class I (H-2Ld)-binding peptide. In transgenic tissue, the H-2Ld/P91A complex is expressed in isolation from other tumor-associated antigens, allowing definition of the immune response to a single defined tumor antigen, a situation closely analogous to events during tumorigenesis. We show that CD8+ T cell immune surveillance of P91A is ineffective without the introduction of a helper determinant operating ...
Complete cancer regression occurs in a subset of patients following adoptive T cell therapy (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs). However, the low success rate presents a great challenge to broader clinical application. To provide insight into TIL-based immunotherapy, we studied a successful case of ACT where regression was observed against tumors carrying the hotspot mutation G12D in the KRAS oncogene. Four T cell receptors (TCRs) made up the TIL infusion and recognized two KRAS-G12D neoantigens, a nonamer and a decamer, all restricted by human leukocyte antigen (HLA) C*08:02. Three of them (TCR9a, 9b, and 9c) were nonamer-specific, while one was decamer-specific (TCR10). We show that only mutant G12D but not the wild-type peptides stabilized HLA-C*08:02 due to the formation of a critical anchor salt bridge to HLA-C. Therapeutic TCRs exhibited high affinities, ranging from nanomolar to low micromolar. Intriguingly, TCR binding affinities to HLA-C inversely correlated ...
Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4 + interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology. © 2012 Nature America, Inc. ...
The data presented here point to an active cooperation between CD4+ and CD8+ T cells in the eradication of tumor cells. The adoptive transfer of CD4+ T cells has been reported to treat established tumor (17, 18, 19); however, CD4+ T cells in these systems were hypothesized to act through NK or macrophage effector cells or by direct lysis of a MHC class II-positive tumor. Ossendorp et al. have found that generation of specific CD4+ T cells through immunization with a helper epitope resulted in increased anti-tumor activity that is mediated by CD8+ effector cells, even when the tumor cells used are MHC class II negative (20). The present manuscript is the first in which the transfer of CD4+ T cells specific for a model tumor Ag have been found to elicit the de novo generation of CD8+ T cells specific for that same Ag.. CD8+ T cells have been widely reported to transfer tumor immunity and to treat established tumors upon adoptive transfer (21, 22). They are thought to work by directly destroying ...
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My research has focused on the discovery and clinical development of novel cancer immunotherapeutics targeting the self/tumor antigen guanylyl cyclase C (GUCY2C; GCC). Current research projects focus on:. 1. Cancer Mucosa Antigens as Immunotherapeutic Targets for Metastatic Tumors. Immunotherapy for human cancers is hindered, in part, by a lack of suitable target antigens. This is particularly relevant in tumors derived from mucosal tissues such as colorectal cancer, in which antigens that are sufficiently immunogenic, tumor-restricted and shared among patients are lacking, and for which conventional therapeutics are poorly efficacious. We have explored a novel class of tumor-associated antigens fulfilling these criteria by exploiting immune compartmentalization, which restricts cross-talk between systemic and mucosal immune compartments. This compartmentalization limits systemic tolerance to mucosa-restricted self-antigens and shields mucosa from systemic autoimmune responses. Thus, a novel ...
Antibody Panel to Epithelial Cell Surface Antigen EpCAMAcris Antibodies offers a full range of thoroughly evaluated antibodies for specific detection…
Interleukin 1 Receptor Associated Kinase 4 (Renal Carcinoma Antigen NY REN 64 or IRAK4 or EC 2.7.11.1) - Pipeline Review, H1 2019
This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. This MAGEA gene encodes a protein that is C-terminally truncated compared to other family members, and this gene can be alternatively interpreted to be a pseudogene. The protein is represented in this Gene record in accordance with the assumed protein-coding status defined in the literature. Read-through transcription exists between this gene and the upstream melanoma antigen family A, 10 (MAGEA10) gene.
NY-ESO-1 and LAGE-1 are cancer testis antigens with an ideal profile for tumor immunotherapy, combining up-regulation in many cancer types with highly restricted expression in normal tissues and sharing a common HLA-A*0201 epitope, 157-165. Here, we present data to describe the specificity and anti-tumor activity of a bifunctional ImmTAC, comprising a soluble, high-affinity T-cell receptor (TCR) specific for NY-ESO-1157-165 fused to an anti-CD3 scFv. This reagent, ImmTAC-NYE, is shown to kill HLA-A2, antigen-positive tumor cell lines, and freshly isolated HLA-A2- and LAGE-1-positive NSCLC cells. Employing time-domain optical imaging, we demonstrate in vivo targeting of fluorescently labelled high-affinity NYESO-specific TCRs to HLA-A2-, NYESO- 1157-165-positive tumors in xenografted mice. In vivo ImmTAC-NYE efficacy was tested in a tumor model in which human lymphocytes were stably co-engrafted into NSG mice harboring tumor xenografts; efficacy was observed in both tumor prevention and ...
Sigma-Aldrich offers abstracts and full-text articles by [Achim A Jungbluth, Scott Ely, Maurizio DiLiberto, Ruben Niesvizky, Barbara Williamson, Denise Frosina, Yao-Tseng Chen, Nina Bhardwaj, Selina Chen-Kiang, Lloyd J Old, Hearn Jay Cho].
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Tumor-associated antigens (TAA) are monomorphic self-antigens that are proposed as targets for immunotherapeutic approaches to treat malignancies. We investigated whether T cells with sufficient avidity to recognize naturally overexpressed self-antigens in the context of self-HLA can be found in the T-cell repertoire of healthy donors. Minor histocompatibility antigen (MiHA)-specific T cells were used as model, as the influence of thymic selection on the T-cell repertoire directed against MiHA can be studied in both self (MiHApos donors)and non-self (MiHAneg donors) backgrounds. T-cell clones directed against the HLA*02:01-restricted MiHA HA-1H were isolated from HA-1Hneg/HLA-A*02:01pos and HA-1Hpos/HLA-A*02:01pos donors. Of the 16 unique HA-1H-specific T-cell clones, 5 T-cell clones derived from HA-1Hneg/HLA-A*02:01pos donors and 1 T-cell clone derived from an HA-1Hpos/HLA-A*02:01pos donor showed reactivity against HA-1Hpos target cells. Additionally, in total 663 T-cell clones (containing at ...
The human MAGE genes are expressed in a wide variety of tumors but not in normal cells, with the exception of the male germ cells, placenta, and, possibly, cells of the developing embryo. These genes encode tumor-specific antigens recognized by cytolytic T lymphocytes. The MAGE genes are located on …