• anti-tumor
  • We were surprised by the anti-tumor effect of these CD4 T cells and its duration of response," Yee said. (bio-medicine.org)
  • Yee and colleagues theorized that infusion of a massive dose of CD4+ T cells would persist longer in the body because they make their own growth factor, interleukin 2, while stimulating the anti-tumor effect of the patient's existing CD8+ T cells. (bio-medicine.org)
  • However, until recently there was no feasible way to isolate and expand anti-tumor CD4+ T cells in the lab. (bio-medicine.org)
  • however, there exists a paucity of knowledge on the precise anti-tumor action of IFN- α / β at the cellular and molecular levels in cutaneous malignancies such as SCC, BCC, and melanoma. (hindawi.com)
  • Discovery that the administration of anti-tumor T lymphocytes (TIL) could mediate the regression of established metastatic melanoma in humans (N. Engl. (ki.se)
  • This work used anti-tumor T lymphocytes genetically engineered to express a marker gene (neomycin phosphotransferase) to track the distribution of T-cells after infusion to patients and opened the door to the field of human gene therapy (N. Engl. (ki.se)
  • Dr. Rosenberg was the first to discover successful gene therapy of a non-melanoma solid cancer in humans using genetically engineered lymphocytes encoding an anti-tumor T-cell receptor targeting the NY-ESO-1 cancer-germline antigen in patients with sarcomas (J. Clin. (ki.se)
  • Discovery that anti-tumor T cells targeting unique somatic immunogenic cancer mutations could lead to the regression of a common human epithelial cancer (Science 344:641-645, 2014). (ki.se)
  • Blood samples containing the required precursors for CD4+ helper T-cell, CD8+ cytotoxic T-cell, and natural killer (NK) cell are extracted from the patient and activated before being re-administered to the patient to induce anti-tumor activity. (wikipedia.org)
  • This method of activation may be used for the preparation of anti-tumor vaccines or for ex vivo activation of the cytotoxic T-cells which can then be followed by the expansion of T-cells through normal, mature dendritic cells. (wikipedia.org)
  • peptide
  • Basically, this strategy relies on the isolation of the genes encoding the α and β chains of a TCR specific for an antigen from a T-cell clone (e.g., from tumor-infiltrating lymphocytes (TILs), peptide-stimulated PBLs from healthy individuals or from immunized human leukocyte antigen (HLA)-transgenic mouse). (frontiersin.org)
  • The first structures of peptide/MHC-I structures illustrated how peptides were presented by MHC-I proteins, lying in an extended form embedded within a binding groove formed by two flanking α helices and a β sheet floor ( 1 ). (frontiersin.org)
  • The solution of peptide/MHC-I structures answered fundamental questions in immunology, including how a single receptor can simultaneously recognize both self (MHC) and non-self (peptide) in antigen recognition ( 2 ). (frontiersin.org)
  • The first high-resolution crystal structure of a TCR-peptide/MHC-I complex was that of the A6 TCR bound to the HTLV-1 Tax 11-19 antigen presented by HLA-A2 ( 3 ). (frontiersin.org)
  • To this aim, we tested an immunotherapy approach encompassing sequential intra-lymph node administration of DNA vectors and peptide analogues to elicit multivalent CD8 + T cell immunity against cancer cell and stromal antigens. (aacrjournals.org)
  • DNA vaccine-primed CD8 + T cells showed a coordinated, lower expression of co-inhibitory molecule PD-1 and retention of the lymph node homing molecule CD62L, leading to a significant persistence of antigen-specific T cells, cellular expansion and functional conversion to effector cells, upon peptide boosting. (aacrjournals.org)
  • Peptide antigens expressed on the surface of cancer cells have been shown in multiple studies to induce T-cell recognition leading to tumor cell killing and/or the release of helper cytokines ( 8 , 9 ). (aacrjournals.org)
  • We compared the frequencies of circulating suppressive Treg and MDSC on-study to baseline levels, as well as frequencies of CD4+ and CD8+ T cells specific to shared tumor-associated antigens (Gp-100, MART-1, NY-ESO-1) utilizing overlapping peptide libraries (15-mer peptides overlapping by 4). (aacrjournals.org)
  • This peptide can originate from a protein that remains within the cell (Fig. 1). (wikipedia.org)
  • In other instances, the normal peptide is presented at the cell surface and consequently the T lymphocytes that recognize the antigen have been eliminated by the central tolerance process that occurs in the thymus. (wikipedia.org)
  • This is due to the fact that its precursor frequency among cytotoxic T-cells is one of the highest known so far, making it easy for antigen presenting cells to evoke peptide-specific responses. (wikipedia.org)
  • receptor
  • Type I interferons (IFN- α , IFN- β ) bind to cell surface receptors with two distinct subunits: IFN- α receptor 1 and IFN- α receptor 2. (hindawi.com)
  • This binding triggers phosphorylation of janus kinase 1 (JAK1) and tyrosine kinase 2 (TK2), members of the Janus kinase family of receptor-associated tyrosine kinases. (hindawi.com)
  • We demonstrate using human melanoma cell lines that this resistance phenotype can be induced in vitro by treatment with MART1 T cell receptor-expressing T cells or with TNFα, and that the phenotype is reversible with withdrawal of inflammatory stimuli. (aacrjournals.org)
  • In 2006 administration of normal circulating lymphocytes transduced with a retrovirus encoding a T-cell receptor (TCR) that recognized the MART-1 melanoma-melanocyte antigen, mediated tumor regression. (wikipedia.org)
  • In 2010 administration of lymphocytes genetically engineered to express a chimeric antibody receptor (CAR) against B cell antigen CD19 was shown to mediate regression of an advanced B cell lymphoma. (wikipedia.org)
  • Disclosed herein is a method for modulating Program Death Receptor Ligand 1 (PDL1) in a cancer cell, comprising contacting the cell with a composition comprising a histone deacetylase (HDAC) inhibitor. (patents.com)
  • Also disclosed is a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a histone deacetylase (HDAC) inhibitor and a composition comprising a therapeutically effective amount of a Program Death Receptor Ligand 1 (PDL1) inhibitor, a Programmed Death 1 receptor (PD1) inhibitor, or a combination thereof. (patents.com)
  • This occurs because each T cell is endowed with a highly specific receptor that can bind to an antigen present at the surface of another cell. (wikipedia.org)
  • There a process named central tolerance eliminates the T cells that have a receptor recognizing an antigen present on normal cells of the organism. (wikipedia.org)
  • solid tumors
  • Although such approaches are relatively nontoxic and have resulted in increased numbers of circulating antigen-specific T cells in peripheral blood (especially after long series of vaccinations over many months), rarely have they led to objective regressions of bulky, established solid tumors ( 18 - 23 ). (aacrjournals.org)
  • epitopes
  • We confirmed the validity of the in vivo model by showing that the melan-A-specific (MART-1-specific) TCR DMF5 induces rejection of tumors expressing analog, but not native, MART-1 epitopes. (jci.org)
  • Claim 27 related to a recombinant polypeptide comprising a P.falciparum antigen and a string of two or more malarial CD8+ T cell epitopes selected from specific amino acid sequences. (epo.org)
  • responses
  • Follow-up tests showed T cell responses to two additional tumor antigens, MAGE-3 and MART-1. (bio-medicine.org)
  • The failure of activated T cells to consistently induce clinical responses in many other patients has pushed us toward a deeper understanding of natural immunoregulatory mechanisms that are directly responsible for diminishing tumor-specific T-cell activation, migration, and effector function in vivo . (aacrjournals.org)
  • Such immunosuppressive factors likely evolved to prevent autoimmunity, but are frequently co-opted by tumors to evade tumor-specific immune responses. (aacrjournals.org)
  • It is a multifunctional cytokine, the properties of which bridge innate and adaptive immunity, acting as a key regulator of cell-mediated immune responses through the induction of T helper 1 differentiation. (aacrjournals.org)
  • This is supported by the analysis of numerous animal ( 1 , 2 ) and human clinical studies that attribute improved clinical outcome ( 3 ) and mechanisms of IL-12-based therapy ( 4 ) to strong type 1 responses in situ . (aacrjournals.org)
  • In addition to its noted effects in the priming of T helper 1 (TH1) cell responses and IFN-γ production by T and natural killer (NK) cells, more recent studies support its critical role as a third signal for CD8 + T cell differentiation ( 5 , 6 ), and its ability to serve as an important factor in the reactivation and survival of memory CD4 + T cells ( 7 ). (aacrjournals.org)
  • It is now proven that tumor-specific antigens exist and that patients mount spontaneous T cell responses against such antigens. (wikipedia.org)
  • The purpose of T cell-mediated cancer immunotherapy is to reactivate these responses to a degree that results in tumor destruction without causing harmful effects on normal cells. (wikipedia.org)
  • In cancer patients, about one half of the highly tumor-specific antigens recognized by spontaneous T cell responses are encoded by mutated genes, the other half being encoded by cancer-germline genes. (wikipedia.org)
  • effector
  • With this knowledge, it now becomes imperative to develop specific clinical interventions capable of eliminating tumor-specific immunosuppression, with the goal of shifting the balance to favor effector T-cell function and tumor cell killing. (aacrjournals.org)
  • CTLs and NK cells are both effector cells so helper T-cells (Th) are also prepared in order to create memory cells for long term resistance toward tumor cells. (wikipedia.org)
  • human
  • SEATTLE, June 18 /PRNewswire/ -- Researchers describe the first successful use of a human patient's cloned infection-fighting T cells as the sole therapy to put an advanced solid-tumor cancer into long-term remission. (bio-medicine.org)
  • Fas- and activation-induced apoptosis are reduced in human T cells preactivated in the presence of TGF-beta 1. (jimmunol.org)
  • patients must be type human leukocyte antigens (HLA-A)*0201, the type on which this vaccine is based. (clinicaltrials.gov)
  • Mutated genes contribute greatly to the immunogenicity of human tumors. (wikipedia.org)
  • peripheral
  • Still, the isolation of such antigen-specific T-cells is not always possible and as such, alternative approaches have been designed to enable the generation of antigen-specific lymphocytes from peripheral T-cells. (frontiersin.org)
  • had successfully produced a soluble fusion protein of LAG3 and immunoglobulin around 1995 and had initially envisaged its use as an immunosuppressant after evidence that its interaction with MHC class II molecules leads to the down-regulation of CD4+ antigen-specific T cell clone proliferation and cytokine secretion, and that it inhibited the alloresponses of naive peripheral blood lymphocytes. (wikipedia.org)
  • A potential mechanism of antigen-specific peripheral lymphocyte deletion. (jimmunol.org)
  • molecular
  • 1 Molecular Cell Biology and Gene Therapy, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. (jci.org)
  • Although such tolerance mechanisms have emerged as formidable barriers to immunotherapy, as discussed below, our knowledge of tumor-associated antigens for melanoma and other tumor types has provided potential molecular targets for T cell-based immunotherapy, and has allowed for the design of strategies to break immune tolerance for patients with cancer. (aacrjournals.org)
  • patients
  • If proven successful in more patients, Yee predicted this therapy could be used for the 25 percent of all late-stage melanoma patients who have the same immune-system type and tumor antigen. (bio-medicine.org)
  • Secondly, both objective tumor regression and elevation of antigen-specific T cells were observed in immunized patients, although there was no strict correlation between these two outcomes. (aacrjournals.org)
  • After every other treatment course (every 6 months), patients will undergo a series of x-rays and scans to look for tumor. (clinicaltrials.gov)
  • Patients are monitored for 1 hour after each injection and have blood tests and a physical examination to look for treatment side effects. (clinicaltrials.gov)
  • Patients whose disease returns during the first course of vaccine therapy will have surgery to remove the tumor and will continue to receive the vaccine treatment. (clinicaltrials.gov)
  • 1994
  • The names MART-1 and melan-A were coined by two groups of researchers who independently sequenced the gene for this antigen in 1994. (wikipedia.org)
  • molecules
  • A class of genes, named cancer-germline genes, is expressed in a large variety of cancer cells but not in normal cells, with the exception of germline cells, which do not carry MHC molecules on their surface and therefore do not present the antigens. (wikipedia.org)
  • immunity
  • Interleukin-12 (IL-12) is recognized as a master regulator of adaptive type 1, cell-mediated immunity, the critical pathway involved in protection against neoplasia and many viruses. (aacrjournals.org)
  • melanomas
  • The contribution of these antigens to tumor immunogenicity is expected to vary according to the mutation rate: higher in lung carcinomas arising in tobacco smokers, in melanomas owing to mutations induced by UV and in the 15% of colorectal carcinomas that have hypermutated DNA owing to defects in the DNA mismatch repair pathway. (wikipedia.org)
  • gene
  • Gene Expression גלובל ניתוח באמצעות פלטפורמה דג הזברה microarray oligonucleotide Samuel M. Peterson 1 , Jennifer L. Freeman 1 1 School of Health Sciences, Purdue University Microarrays ג'ין הם כלים רבי עוצמה באפיון ביטוי גנים ברמת הגנום כולו. (jove.com)
  • The same name is also used to refer to the gene which codes for the antigen. (wikipedia.org)
  • mutations
  • In a syngeneic HLA-A2-transgenic mouse model of large established tumors, we found that both mutations differed dramatically as targets for TCR-modified T cells in vivo. (jci.org)
  • mice
  • A June 2000 paper in the Journal of Immunology showing that IMP321 would act as a vaccine adjuvant when immunizing mice with hepatitis B surface antigen and soluble ovalbumin. (wikipedia.org)
  • High doses of IL-2 could inhibit tumor growth in mice. (wikipedia.org)