• Although B cell receptors can also recognize MHCs, immune responses seem to only be elicited by T cells. (wikipedia.org)
  • However, there is death by apoptosis of thymocytes that do not interact with MHC molecules or have high-affinity receptors for self MHC plus self antigen a process referred to as negative selection. (wikipedia.org)
  • The genetic transfer of T-cell receptors (TCRs) directed toward target antigens into T lymphocytes has been used to generate antitumor T cells efficiently without the need for the in vitro induction and expansion of T cells with cognate specificity. (fujita-hu.ac.jp)
  • These data implicate that T cells with high-affinity antigen receptors reduce the ability to lyse targets with low-density peptide/MHC complexes (∼100 per cell), while they could respond at cytokine production level. (fujita-hu.ac.jp)
  • Besides the secretion of pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), the increased expression of receptor repertoire (pattern recognition receptors, PRR) on APCs, mostly macrophages and dendritic cells, occurs as a result of the release of endogenous and exogenous antigens (damage-associated molecular patterns, DAMPs, and pathogen-associated molecular patterns, PAMPs). (hindawi.com)
  • Class II major histocompatibility complex mutant mice to study the germline bias of T cell antigen receptors. (nationaljewish.org)
  • An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. (elevate.bio)
  • MHC restriction reflects the fact that the effector function of T cells is determined by the kind of Self-H recognized together with the foreign antigen on cell surfaces: K and D are receptors for lytic signals, I determinants are receptors for cell differentiation signals that are delivered antigen-specifically by T cells. (typeset.io)
  • His current scientific interest focusses on the role of indirect recognition of mismatched HLA in transplantation and on post-transplant immunomonitoring via Next Generation Sequencing of T- and B-cell receptors and immunoglobulins. (umcutrecht.nl)
  • The crystal structure of human and murine T cell receptors (TcRs) specific for immunodominant viral peptides presented to cytotoxic T cell (CTL) suggests that the central region of the peptide is critical for TcR contacts and that aromatic rings are accommodated in a small cavity determined by the variable CDR3 region of the TcR ( 7 , 8 ). (silverchair.com)
  • Phenotypic and functional alterations in lupus T cells including expansion of the Th17 population, perturbations of the physiology of T-cell receptors (TCRs) and postreceptor downstream signalling, oxidative stress, and epigenetic changes result in exaggeration of TCR response to stimuli and the propensity of lupus T cells to get activated [ 6 ]. (hindawi.com)
  • Although graft or bone marrow rejection can have detrimental effects, there are immunotherapy benefits when cytotoxic T lymphocytes are specific for a self antigen and can target antigens expressed selectively on leukemic cells in order to destroy these tumor cells referred to as graft-versus- leukemia effect (GVL). (wikipedia.org)
  • The implication of these results would be that myeloma-specific T cell subfamilies might be positively selected from the donor inoculum and infused to myeloma patients post ASCT, to afford separation of allo- from tumor-reactive T cells without the prior need to define specific target antigens. (biomedcentral.com)
  • This phase I trial assessed the safety, efficacy, and immunologic responses to minor histocompatibility antigens following nonmyeloablative allogeneic hematopoietic cell transplantation as treatment for metastatic renal cell carcinoma. (aacrjournals.org)
  • Eight patients received conditioning with fludarabine and low-dose total body irradiation followed by hematopoietic cell transplantation from an HLA-matched sibling donor. (aacrjournals.org)
  • Treatment of metastatic renal cell carcinoma with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning with fludarabine/total body irradiation is feasible and may induce tumor regression or stabilization in some patients. (aacrjournals.org)
  • [ 1 ] Acute GVHD describes a distinctive syndrome of dermatitis (see the image below), hepatitis, and enteritis developing within 100 days after allogeneic hematopoietic cell transplantation (HCT). (medscape.com)
  • Kelly Olsen defended her doctoral dissertation, Shared Minor Histocompatibility Antigen Discovery and Targeting in the Context of Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies. (unc.edu)
  • The efficacy of allogeneic hematopoietic cell transplantation (HCT) in hematologic malignancies can in large part be attributed to a graft-versus-tumor (GVT) effect, by which the donor immune system achieves immunologic control of the tumor. (mhmedical.com)
  • Dr. Al Malki is an Associate Professor in the Department of Hematology & Hematopoietic Cell Transplantation and Director of the Unrelated Donor Bone Marrow Transplant and Haploidentical Transplant Programs at City of Hope. (tscan.com)
  • Heme Malignancies Program: TScan's two lead TCR-T cell therapy candidates, TSC-100 and TSC-101, are designed to target HA-1 and HA-2, respectively, to treat residual disease and prevent relapse in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS) patients undergoing allogeneic haploidentical hematopoietic cell transplantation (HCT) with reduced intensity conditioning (RIC). (tscan.com)
  • The International Histocompatibility Working Group (IHWG) is a collaborative international effort to increase the availability and efficacy of hematopoietic cell transplantation (HCT) from alternative donors through an improved understanding of the genetic barrier. (ihiw18.org)
  • The HCT working group is comprised of experts in the fields of histocompatibility and immunogenetics, hematopoietic cell transplantation, and outcomes research. (ihiw18.org)
  • We show that immunization of HLA-A2 transgenic mice with tetramerized recombinant HLA-A2 incorporating HA-1 H minor histocompatibility antigen (mHag) peptides and β2- microglobulin (HA-1 H/HLA-A2) generate highly specific antibodies. (fujita-hu.ac.jp)
  • Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance. (imperial.ac.uk)
  • Metal-specific CD4+ T-cell responses induced by beryllium exposure in HLA-DP2 transgenic mice. (nationaljewish.org)
  • IL-20 deficiency was associated with increased IFN/STAT2 activity in mice and IFN/STAT2-induced necroptotic cell death in IEC-derived organoids could be markedly blocked by IL-20. (bvsalud.org)
  • Immunization of female C57BL/6 mice with splenocytes from male H60H Tg induced a CD8 T cell primary response and memory respon-se after re-challenge. (molcells.org)
  • Bone marrow cells from C3H (H-2k) mice, a strain that does not exhibit cross-reactive lysis of trinitrophenyl (TNP)-modified allogeneic targets, were allowed to mature in heavily irradiated (B6 times C3H)F1 (H-2b/k) recipients, an F1 hybrid that does demonstrate cross-reactive lysis. (typeset.io)
  • Spleen cells from these chimeric mice were removed after 3-4 mo and by H-2 typing shown to be of C3H origin. (typeset.io)
  • Administration of this oligonucleotide, but not of a control oligonucleotide lacking this motif, to mice led to the disappearance of DC from the marginal zone and T-cell areas of spleen, but not from heart or kidney. (ox.ac.uk)
  • We used two-photon microscopy to simultaneously track antigen-specific OT-II T cells, nonspecific T cells and DCs in lymph nodes of living mice. (ox.ac.uk)
  • Potential effects of forced CD20 expression on T-cell function were investigated by comparing CD20- and mock-transduced cytomegalovirus (CMV) specific T cells for cytolysis, cytokine release and proliferation. (haematologica.org)
  • Regulatory vs. inflammatory cytokine T-cell responses to mutated insulin peptides in healthy and type 1 diabetic subjects. (nationaljewish.org)
  • No significant toxicities attributed to the T cells have been observed, including no infusion reactions or evidence of cytokine release syndrome or graft versus host disease. (elevate.bio)
  • Because the cytokine profile of Th cells is often regulated by dendritic cells (DC), we studied the modulatory effects of GA on the T cell regulatory function of human DC. (aai.org)
  • DC exposed to GA induce effector IL-4-secreting Th2 cells and enhanced levels of the anti-inflammatory cytokine IL-10. (aai.org)
  • Finally, we show that MAIT cells are highly proliferative in response to antigenic and cytokine stimulation, maintaining high expression of GrB, perforin, and GrA, but reduced expression of GrK following antigenic proliferation. (ox.ac.uk)
  • Active investigation is in progress in 8 key areas: the impact of HLA matching, role of race and ethnicity, identification of permissible HLA mismatches, haplotype-associated determinants, minor histocompatibility antigens, non-inherited maternal antigens, immune response and cytokine genes, and KIR genetics. (ihiw18.org)
  • Alternatively, T cells have been gene-modified with a TCR-like antibody or chimeric antigen receptor (CAR). (fujita-hu.ac.jp)
  • The use of CD20 as suicide gene was investigated in CMV specific T cells and in T cells genetically modified with an antigen specific T-cell receptor. (haematologica.org)
  • CD20-transduced T cells with and without co-transferred T-cell receptor were efficiently eliminated by complement dependent cytotoxicity induced by therapeutic anti-CD20 antibody rituximab. (haematologica.org)
  • T-cell receptor (TCR) gene transfer is an attractive strategy for rapid in vitro generation of high numbers of antigen specific T cells. (haematologica.org)
  • We used an MHC-matched/miHA-disparate B10.D2 → Balb/c bone marrow transplantation (BMT) murine model and MOPC315.BM MM cells to develop an ATCT protocol consisting of total body irradiation, autologous-BMT and infusion of selective, myeloma-reactive lymphocytes of T cell receptor (TCR) Vβ 2, 3 and 8.3 families (MM-auto BMT ATCT). (biomedcentral.com)
  • In this regard, immune-transcriptome analyses of T cell receptor (TCR) Vβ CDR3-size and sequence is being used to characterize alloreactive versus tumor-specific T-cell responses. (biomedcentral.com)
  • Cambridge, Mass. - December 6, 2020 - HighPassBio, an ElevateBio portfolio company dedicated to advancing novel targeted T cell immunotherapies, today discussed the ongoing Phase 1 trial of the company's lead product candidate, an engineered T cell receptor (TCR) T cell therapy targeting HA-1 expressing cancer cells in an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting. (elevate.bio)
  • TScan is a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR) engineered T cell therapies (TCR-T) for the treatment of patients with cancer. (tscan.com)
  • WALTHAM, Mass., Nov. 09, 2023 (GLOBE NEWSWIRE) -- TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer, today reported financial results and provided a corporate update for the third quarter ended September 30, 2023. (tscan.com)
  • Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. (cnrs.fr)
  • PITTSBURGH, PA, February 6, 2023 - BlueSphere Bio , a T-cell receptor (TCR) T-cell therapy company developing a powerful TCR discovery platform and novel therapeutic candidates for patients with hematologic malignancies and solid tumors, today announced Keir Loiacono, Chief Executive Officer of BlueSphere Bio, will present a corporate overview at the 2023 BIO CEO & Investor Conference held in New York City, NY from February 6-9, 2023. (bluespherebio.com)
  • or actively by prior immunization of the recipient with graft antigens which evoke specific antibodies and form antigen-antibody complexes which bind to the antigen receptor sites of the T-cells and block their cytotoxic activity. (lookformedical.com)
  • Here we demonstrate that by using glycopeptides with high affinity for the major histocompatibility complex and glycosylated in a position corresponding to a critical T cell receptor (TcR) contact, it is possible to induce anti-TACA CTL in vivo. (silverchair.com)
  • Here, potential mechanisms involving alterations in T-cell receptor expressions, postreceptor downstream signalling, epigenetics, and oxidative stress which favour activation of lupus T cells will be discussed. (hindawi.com)
  • They cause problems of rejection less frequently than those of the major histocompatibility complex (MHC). (wikipedia.org)
  • Here, we show that even expression of minor histocompatibility (mH) antigens is sufficient to provoke acute rejection of tissues differentiated from ES cells. (ox.ac.uk)
  • Cutting Edge: Roles for Batf3-Dependent APCs in the Rejection of Minor Histocompatibility Antigen-Mismatched Grafts. (nationaljewish.org)
  • Long-term engraftment of allogeneic cells necessitates eluding immune-mediated rejection, which is currently achieved by matching for human leukocyte antigen (HLA) expression, immunosuppression, and/or delivery of donor-derived cells to sanctuary sites. (ashpublications.org)
  • Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (lookformedical.com)
  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT) involves the infusion of stem cells following administration of high-dose chemotherapy or total body irradiation for either tumor control or to prevent solid transplant rejection. (gvhdhub.com)
  • 4 In addition, TCRs for minor histocompatibility antigens, including HA-1 and HA-2, have been transferred to donor-derived virus-specific T cells to treat patients with hematologic malignancies after allogeneic stem cell transplantation. (haematologica.org)
  • TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. (elevate.bio)
  • Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. (elevate.bio)
  • These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the body's immune system to respond to fight off and kill the tumor cells. (elevate.bio)
  • Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease. (elevate.bio)
  • However, some of the TCRs did overlap between the H60H- and H60-specific CD8 T cells, suggesting that H60H might modulate the H60-specific response. (molcells.org)
  • With the recent FDA clearance of our IND for TSC-203-A0201 targeting PRAME, we remain committed to populating the ImmunoBank with TCRs that address different targets and HLA types to expand the reach of multiplexed TCR-T cell therapy. (tscan.com)
  • This platform can be used in various clinical settings to discover TCRs for use in either TCR-based cell therapy or in antibody-like molecules, such as bi-specific T cell engagers. (bluespherebio.com)
  • Concurrent with its use for shared antigens, BlueSphere is deploying TCXpress™ and NEOXpress™, a proprietary patient-specific neoantigen discovery platform, to develop its TCX-201 Program, which aims to identify TCRs reactive against patient-specific neoantigens. (bluespherebio.com)
  • T cells recognize antigens presented to them by the major histocompatibility complex of antigen-presenting cells via the TCRs expressed on their surface. (hindawi.com)
  • Stimulation of TCRs upon antigen binding triggers downstream signalling pathways which enables various physiological functions of the T cells. (hindawi.com)
  • Alcyomics, as a member of the Northern Alliance for Advanced Therapies Treatment Centre (NA-ATTC) has conducted safety assessments on two novel cellular products, an anti COVID T-Cell specific product and assessment of the safety of peptides for use in a tolerogenic dendritic cell therapy for the treatment of rheumatoid arthritis. (alcyomics.com)
  • Dendritic cells (DC) 3 make up a family of highly specialized cells that upon activation by pathogens or their products mature into professional APC. (aai.org)
  • class II are expressed on specialized antigen-presenting cells (APCs), such as macrophages, dendritic cells, and B cells. (mhmedical.com)
  • The effects of DNA containing CpG motif on dendritic cells. (ox.ac.uk)
  • Dendritic cells (DC) are specialized antigen-presenting cells. (ox.ac.uk)
  • Stable T cell-dendritic cell interactions precede the development of both tolerance and immunity in vivo. (ox.ac.uk)
  • The maturation status of dendritic cells (DCs) determines whether they prime or tolerize T cells. (ox.ac.uk)
  • MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. (typeset.io)
  • The result is that the gene complex coding for major transplantation antigens is one of the better understood mammalian genetic regions. (typeset.io)
  • Research and training are largely focused in the areas of immunology, virology, and microbial interactions, but the questions and strategies are broadly based in molecular biology, cell biology, biochemistry, genetics and genomics. (unc.edu)
  • Adam Rosenthal, PhD, assistant professor in the Department of Microbiology and Immunology, shows that genetically identical cells within a bacterial community have different functions, with some members behaving more docile and others producing the very toxins that make us feel ill. (unc.edu)
  • The major focus of the Department of Immunology is on Translational Immunology and its spectrum of basic research covers T cell biology, antibodies, antigen presentation and innate immunity. (immunology-tuebingen.de)
  • One of the major unifying threads in cellular immunology that ended in the identification of MHC-encoded molecules as the Ir gene products and the merging of the two phenomena: Ir gene control and MHC restriction (the requirement for T cells to recognize an MHC-encoded molecule in addition to the antigen in order to become activated). (typeset.io)
  • Nevertheless, despite their immunogenicity in vivo, transplantation tolerance may be readily established by using minimal host conditioning with nondepleting monoclonal antibodies specific for the T cell coreceptors, CD4 and CD8. (ox.ac.uk)
  • A Rapid Method to Characterize Mouse IgG Antibodies and Isolate Native Antigen Binding IgG B Cell Hybridomas. (nationaljewish.org)
  • If you're doing an in vivo or ex vivo T-cell depletion, the incidence of graft-versus-host disease is going to be lower than when you do a T-cell-replete, for which you leave the T cells in the graft, or you don't try to significantly remove them afterward using monoclonal antibodies targeting T cells. (targetedonc.com)
  • As a result, the donor T cells can target the recipients cells called graft-versus-host disease (GVHD). (wikipedia.org)
  • CD8 + CTL-recognizing minor H antigens on tumor cells can be isolated posttransplant and could contribute to the graft- versus -tumor effect. (aacrjournals.org)
  • Adverse side effects, however, may occur and lead to severe autoimmunity or graft-versus-host disease (GvHD), emphasizing the relevance of a suicide mechanism that allows efficient in vivo elimination of infused T cells. (haematologica.org)
  • Requirement for B cells in T cell priming to minor histocompatibility antigens and development of graft-versus-host disease. (google.ca)
  • Graft versus host disease (GVHD), a severe immunogenic complication of allogeneic hematopoietic stem cell transplantation (HSCT), represents the most frequent cause of transplant-related mortality (TRM). (hindawi.com)
  • Criteria used by hematologists/oncologists to diagnose acute graft-versus-host disease (GVHD), and common therapies used for GVHD prevention in patients who receive hematopoietic stem cell transplantation. (targetedonc.com)
  • Risk factors for development of acute graft-versus-host disease depend upon the type of graft you're using-whether it's from an HLA [human leukocyte antigen]-matched sibling versus an HLA-matched unrelated donor, or if you're using a partially matched donor. (targetedonc.com)
  • Therefore, the immune cells that are passively transferred in the stem cell graft are more primed against these minor histocompatibility antigens that are known to be associated with the development of acute graft-versus-host disease. (targetedonc.com)
  • The other major way to prevent graft-versus-host disease is through T-cell depletion, and that can be ex vivo, where the graft, before it's infused, goes through a process, usually through a selection column to remove T cells from the graft. (targetedonc.com)
  • In situ dissection of the graft-versus-host activities of cytotoxic T cells for minor histocompatibility antigens. (alcyomics.com)
  • 4. Qesari M, Richter A, Ogonek J, Mischak-Weissinger E, Wang XN, Dickinson AM. Cytomegalovirus-Specific T Cells Isolated by IFN-γ Secretion Assay Do Not Induce Significant Graft-Versus-Host Reactions In Vitro. (alcyomics.com)
  • Adoptive Allogeneic T-cell therapy (ATCT) might be curative for MM, however current ATCT protocols often lead to graft versus host disease (GvHD). (biomedcentral.com)
  • Transplanting only tumor reactive donor T cells that mediate a graft-versus-myeloma (GvM) but not GvHD may overcome this problem. (biomedcentral.com)
  • Much of the curative potential of allografts is attributed to the graft-versus-tumor (GvT) response that aims to destroy residual tumor cells that persist after induction therapy and ASCT [ 5 ]. (biomedcentral.com)
  • Differentiation of naïve donor T cells into effector cells subsequently occurs, resulting in immunologic attack on host tissues and the potential development of graft-versus-host disease (GVHD) ( 2 ). (mhmedical.com)
  • White blood cells of the donor's immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). (wikipedia.org)
  • The graft usually comes from a human leukocyte antigen (HLA)-matched donor and contains hematopoietic cells as well as immune cells, including T lymphocytes. (gvhdhub.com)
  • Allo-HSCT is an important treatment strategy, which allows administration of myeloablative therapy and the elimination of cancer cells by the transplanted donor T and natural killer (NK) cells in a phenomenon known as the graft- versus -leukemia (GvL) effect. (gvhdhub.com)
  • A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. (elevate.bio)
  • However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. (elevate.bio)
  • Because of these encouraging results, we applied the same antigenic strategy to TACA-containing glycopeptides because induction of a degenerate T cell response against this class of tumor antigens may be of great advantage in cancer immunotherapy ( 10 - 12 ). (silverchair.com)
  • Together, these factors contribute to a state of acquired immune privilege that favors the polarization of infiltrating T cells toward a regulatory phenotype. (ox.ac.uk)
  • The lack of recognition of a T cell to this self antigen is the reason why allogeneic stem cell transplantation for an HLA matched gene or a developing fetus's MiHAs during pregnancy may not be recognized by T cells and marked as foreign leading to an immune response. (wikipedia.org)
  • The recognition of a mature T cell to this self antigen should not induce an immune response. (wikipedia.org)
  • Absence of a costimulatory signal results in T-cell anergy, which is a key mechanism of peripheral immune tolerance to self-antigen in normal immunoregulation. (mhmedical.com)
  • The recipient developed GVHD despite having a HLA- matched genes at the Major Histocompatibility locus. (wikipedia.org)
  • Some of these antigens are ubiquitously expressed in nucleated male cells, and the presence of these antigens has been associated with a greater risk of developing GVHD allogeneic stem cell transplantation for a HLA matched gene when there's a male recipient and female donor. (wikipedia.org)
  • Herpes simplex virus thymidine kinase (HSV-tk) is a well-established suicide gene that has been successfully used to control GvHD following donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation. (haematologica.org)
  • Donor T cells may also induce GvHD due to recognition of allo-antigens on non-malignant tissues of the patient. (haematologica.org)
  • Transfer of HSV-tk to DLI preserves the beneficial anti-tumor effect and allows in vivo elimination of donor T cells if severe GvHD occurs. (haematologica.org)
  • The histocompatibility differences between the donor and the recipient, the presence of donor's immunocompetent cells, and the inability of the recipient to reject these cells were defined as the basic pathogenic prerequisites for GVHD development by Billingham in 1966 [ 10 ]. (hindawi.com)
  • Cytotoxic T lymphocytes were determined as the cellular effectors of GVHD, and the key role of antigen-presenting cells (APCs) in T-lymphocyte activation was established during the following years [ 11 , 12 ]. (hindawi.com)
  • Minor histocompatibility antigen differences likely account for GVHD in HLA-identical sibling stem cell transplants. (unboundmedicine.com)
  • These data demonstrate that a transplantation protocol involving only selective tumor-reactive donor T cell families is an effective immunotherapy and results in long-term survival in a mouse model of human MM. The results highlight the need to develop similar ATCT strategies for MM patients that result in enhanced survival without symptoms of GvHD. (biomedcentral.com)
  • Since GvT responses involve T-cell recognition of tumor-specific peptides presented by MHC molecules [ 14 ], it may be possible to identify and select donor T cells that provide beneficial GvT responses but minimal GvHD risk. (biomedcentral.com)
  • By then infusing the animals with B10.D2 T cells from only the TCR Vβ 2, 3 and 8.3 families appropriately pre-activated in vitro, we saw a vigorous GvM response without any clinical or histological signs of GvHD or disease relapse, which translated into long-term, disease-free survival. (biomedcentral.com)
  • We have a series of clinical trials available to evaluate several different strategies to prevent GVHD, such as T cell depletion and the use of novel immunosuppressive agents. (harvard.edu)
  • However, even in a fully HLA matched HCT, GVHD still occurs due to donor T cells directed against minor histocompatibility antigens (MiHAs), polymorphic peptides displayed on host HLA molecules. (mhmedical.com)
  • GvHD is commonly associated with bone marrow transplants and stem cell transplants . (wikipedia.org)
  • The white blood cells present within the transplanted tissue then attack the recipient's body's cells, which leads to GvHD. (wikipedia.org)
  • GvHD occurs when the donor's immune system's white blood cells reject the recipient. (wikipedia.org)
  • This was developed by the Johns Hopkins University group and has been demonstrated to permit the use of haploidentical stem cell grafts. (targetedonc.com)
  • Although human CD20 has previously been described as functional selection marker and suicide gene after retroviral transfer to T lymphocytes, 9 , 10 the specificities of these T cells were unknown, and therefore a potential effect of CD20 on antigen-specific T-cell functions could not be investigated. (haematologica.org)
  • Compelling evidence has however shown that without the assistance of the helper T lymphocytes, it is indeed difficult for the "helpless" B cells to become functional enough to trigger SLE-related inflammation. (hindawi.com)
  • The female recipient obtained MHC-matched bone marrow cells but still had active cytotoxic T cells (CD8+). (wikipedia.org)
  • Primary human T cells transduced with #131 scFV coupled to CD28 transmembrane and CD3ζ domains were stained with HA-1 H/HLA-A2 tetramers slightly more intensely than a cytotoxic T lymphocyte (CTL) clone specific for endogenously HLA-A2-and HA-1 H-positive cells. (fujita-hu.ac.jp)
  • In conclusion, female UCB comprises HY-specific cytotoxic T cells. (ashpublications.org)
  • This chapter focuses on the important discovery that virus-specific cytotoxic T cells are dually specific for virus and for a self cell surface antigen encoded by the major histocompatibility complex (MHC). (typeset.io)
  • Cytotoxic T-cell specificity is comparable to serological specificity. (typeset.io)
  • Because quantification of specificity or cross-reactivity is difficult, and because of the technical limitations of these cytotoxic T-cell assays, results are interpreted with great reservation. (typeset.io)
  • We show that resting human MAIT cells are uniquely characterized by a lack of granzyme (Gr) B and low perforin expression, key granule proteins required for efficient cytotoxic activity, but high levels of expression of GrA and GrK. (ox.ac.uk)
  • TACA-containing glycopeptides are appealing cytotoxic T cell (CTL)-based vaccines to prevent or treat cancer because the same sugar moieties are expressed in a variety of tumors, rendering a vaccination strategy applicable in a large population. (silverchair.com)
  • MAIT cells are activated by a broad range of bacteria through detection of riboflavin metabolites bound by MR1, but their direct cytolytic capacity upon recognition of cognate target cells remains unclear. (ox.ac.uk)
  • These sanctions were, however, seen as weak by anti for major and minor histocompatibility antigen recognition. (iboard.my)
  • MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells. (wikipedia.org)
  • The presence of immune cells in UCB that are not directed against maternal foreign Ags is remarkable and may explain the reported clinical observation of improved HSCT outcome with younger sibling donors. (ashpublications.org)
  • Allogeneic-donor-derived cells can be genetically modified to eliminate expression of HLA-A. (ashpublications.org)
  • Transplantation between genetically identical individuals, i.e., members of the same species with identical histocompatibility antigens, such as monozygotic twins, members of the same inbred strain, or members of a hybrid population produced by crossing certain inbred strains. (lookformedical.com)
  • The former are genetically determined by the major histocompatibility complex. (bvsalud.org)
  • We describe an immunostimulatory oligonucleotide containing a CpG motif that stimulated murine DC to up-regulate co-stimulatory molecules, induce T-cell proliferative responses and secrete interleukin-12 in vitro. (ox.ac.uk)
  • The consequences of an immune response are seen in allogeneic hematopoietic stem cell transplantation (HCT) when the peptides encoded by polymorphic genes differ between the recipient and the donor T cells. (wikipedia.org)
  • The patient had undergone autologous peripheral blood stem-cell transplantation to treat ovarian cancer. (medscape.com)
  • Allogeneic hematopoietic stem cell transplantation (HSCT) offers the only curative modality for many hematological disorders. (hindawi.com)
  • More recently the same Skimune® platform was used to show the safety and efficacy of anti cytomegalovirus (CMV) T cells used in the treatment of CMV post haematopoietic stem cell transplantation. (alcyomics.com)
  • Despite chemo-induction therapy and autologous stem cell transplantation (ASCT), the vast majority of patients with Multiple Myeloma (MM) relapse within 7 years and the disease remains incurable. (biomedcentral.com)
  • Survival of patients with multiple myeloma (MM) beyond 7 years remains rare even after autologous stem cell transplantation (ASCT) and treatment with novel agents [ 1 ]. (biomedcentral.com)
  • The prognosis for leukemia patients who've relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse," said Elizabeth Krakow, M.D., MSc. (elevate.bio)
  • The abstract for the presentation titled Phase 1 Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress, can be found on the ASH website under the abstract number 137726 . (elevate.bio)
  • The in-person presentation will highlight the Company's first and lead product candidate, BSB-1001, currently being developed for the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myeloid dysplastic syndrome (MDS) in conjunction with allogeneic hematopoietic stem cell transplantation (alloSCT). (bluespherebio.com)
  • BSB-1001, targeting the minor histocompatibility antigen-1 (HA-1) and part of BlueSphere's TCX-101 Program, is the first TCR-T cell therapy candidate generated using TCXpress and is in development for the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myeloid dysplastic syndrome (MDS) in conjunction with allogeneic hematopoietic stem cell transplantation (alloSCT). (bluespherebio.com)
  • His postdoctoral training was performed on minor H antigens in organ- and stem-cell transplantation in the laboratory of Prof. Dr. Els Goulmy, Leiden, The Netherlands. (umcutrecht.nl)
  • the genetic control of immune responses to T cell epitopes with respect to MHC and non-MHC linked genes. (imperial.ac.uk)
  • Rubtsova, K, Rubtsov, AV Halemano K, Sam LX, Kappler JW , Sanitago ML and Marrack P . T cell production of IFNg in response to TLR7/IL12 stimulates optimal B cell responses to viruses. (nationaljewish.org)
  • Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease. (nationaljewish.org)
  • LPS) is a potent factor in infection, which induces M1 macrophages resulting in higher levels of iNOS, TNFα and IL-12p70 which dictate inflammatory T cell responses. (nih.gov)
  • Twenty-three female UCB samples were collected from healthy mothers and analyzed for minor histocompatibility Ag HY-specific responses. (ashpublications.org)
  • The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells. (typeset.io)
  • These peptides are normally around 9-12 amino acids in length and are bound to both the major histocompatibility complex (MHC) class I and class II proteins. (wikipedia.org)
  • Even when a transplant donor and recipient are identical with respect to their major histocompatibility complex genes, the amino acid differences in minor proteins can cause the grafted tissue to be slowly rejected. (wikipedia.org)
  • This chapter opens up with a detailed analysis of the early experiments of these scientists, culminating in the discovery by McDevitt that these genes were linked to the major histocompatibility complex (MHC). (typeset.io)
  • Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell population restricted by the non-polymorphic, major histocompatibility complex class I-related protein 1, MR1. (ox.ac.uk)
  • Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. (lookformedical.com)
  • The fine specificity of the TF-specific CTL repertoire indicates that the TcR recognize the glycosylated amino acid residue together with TF in a conventional major histocompatibility complex class I-restricted fashion. (silverchair.com)
  • Breakdown of immune tolerance is believed to be one of the major mechanisms which triggers the production of autoantibodies by B cells and antibody forming cells, leading to inflammation upon binding to autoantigens and consequent tissue damage [ 2 ]. (hindawi.com)
  • Clinically, the number and size of the ulcers are the two main criteria used to divide ulcers into three forms: minor, major, and herpetiform. (medscape.com)
  • In contrast, complex aphthosis has a severe clinical course, with an almost continuous presence of minor or major ulcers. (medscape.com)
  • A group of antigens that includes both the major and minor histocompatibility antigens. (bvsalud.org)
  • Patients were monitored for donor engraftment of myeloid and lymphoid cells, for clinical response by serial imaging, and for immunologic response by in vitro isolation of donor-derived CD8 + CTLs recognizing recipient minor histocompatibility (H) antigens. (aacrjournals.org)
  • 1 , 2 The anti-tumor effect of DLI is mediated by donor T cells recognizing allo-antigens on the malignant cells of the recipient. (haematologica.org)
  • An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. (lookformedical.com)
  • 100-fold higher antigen density to exert cytotoxicity compared with the cognate CTL clone, they could produce inflammatory cytokines against cells expressing HLA-A2 and HA-1 H transgenes. (fujita-hu.ac.jp)
  • These cells were found to be tolerant to B6 alloantigens by mixed lymphocyte reaction and cell-mediated cytotoxicity and, when stimulated in vitro with TNP-modified syngeneic cells, now cross-reactively lysed TNP-modified allogeneic targets. (typeset.io)
  • Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patient's native cells, and not by the cells from the stem cell transplant donor. (elevate.bio)
  • Macrophages are heterogeneous cell populations that are present in all tissues. (nih.gov)
  • CD11c-Expressing B Cells Are Located at the T Cell/B Cell Border in Spleen and Are Potent APCs. (nationaljewish.org)
  • helper T cells produce further cytokines, especially IL-2, and prime host APCs via CD40:CD40L interaction. (mhmedical.com)
  • In phase I, chemotherapy or radiotherapy as part of transplant conditioning causes host tissue damage and release of inflammatory cytokines such as TNF-α, IL-1, and IL-6, with resulting priming of host antigen-presenting cells (APCs). (mhmedical.com)
  • T-cell activation requires costimulatory signals from the APC, specifically CD80/86 binding to CD28 or LFA-3 binding to CD2 ( 1 ). (mhmedical.com)
  • Bacterial activation of MAIT cells rapidly induced GrB and perforin, licensing these cells to kill their cognate target cells. (ox.ac.uk)
  • Thus, early antigen-dependent T cell arrest on DCs is a shared feature of tolerance and priming associated with activation and proliferation. (ox.ac.uk)
  • Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. (lookformedical.com)
  • During the third quarter, TScan announced U.S. Food and Drug Administration (FDA) clearance of its investigational new drug (IND) application for TSC-203-A0201, a TCR-T targeting PReferentially expressed Antigen in MElanoma (PRAME). (tscan.com)
  • Finally, overexpression of TRIM28 or knock-out of TRIM17 reduced BCLA1 protein levels and restored sensitivity of melanoma cells to BRAF-targeted therapy. (edu.au)
  • CD8 + CTL clones recognizing minor H antigens were isolated from five patients studied. (aacrjournals.org)
  • Clones from three patients with a partial response or stable disease recognized antigens expressed on renal cell carcinoma tumor cells. (aacrjournals.org)
  • T-cell clones were stimulated every 10-14 days with irradiated allogeneic PBMC and phyto-hemagglutinin in IMDM with 5% human serum (HS), 5% FBS and 100 IU/mL IL-2 as previously described. (haematologica.org)
  • Forty-two of 104 tetramer pos T-cell clones, isolated from 16 of 17 UCB samples, showed male-specific lysis in vitro. (ashpublications.org)
  • The Skimune® platform has been shown to demonstrate the specificity of T-cell clones developed for use in the treatment of leukaemia and the work was published in Nature Medicine in 2002 (3 and 4). (alcyomics.com)
  • HLA-identical sibling stem cells are used for the treatment of patients suffering from various hematologic malignant and nonmalignant diseases. (ashpublications.org)
  • Minor histocompatibility antigen (also known as MiHA) are peptides presented on the cellular surface of donated organs that are known to give an immunological response in some organ transplants. (wikipedia.org)
  • We further used RNA-sequencing (RNA-Seq), RNAScope and Gene Ontology analysis, western blot analysis and co-immunoprecipitation, confocal microscopy and intestinal epithelial cell (IEC)-derived three-dimensional organoids to investigate the underlying molecular mechanisms. (bvsalud.org)
  • Although human embryonic stem (ES) cells may one day provide a renewable source of tissues for cell replacement therapy (CRT), histoincompatibility remains a significant barrier to their clinical application. (ox.ac.uk)
  • DC can acquire and process antigens in the periphery before maturing and migrating to secondary lymphoid tissues where they present the antigens and deliver co-stimulatory signals to T cells. (ox.ac.uk)
  • 1). Numerous studies indicate that some TACA are expressed on a variety of neoplastic tissues ( 2 - 6 ) and not normally expressed in differentiated cells, suggesting their suitability as a candidate for vaccine therapy. (silverchair.com)
  • The aim of adoptive T-cell therapy of cancer is to selectively confer immunity against tumor cells. (haematologica.org)
  • The CD8+ T cells were active and targeted the male bone marrow cells. (wikipedia.org)
  • The male bone marrow cells were found to be presenting a peptide in the MHC groove encoded by a gene on Y chromosome. (wikipedia.org)
  • Patient characteristic data was shared in the oral presentation at ASH, including documented HA-1 TCR T cell persistence in blood and bone marrow up to 18 months. (elevate.bio)
  • Antiviral CD8 + T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion. (nationaljewish.org)
  • Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR. (nationaljewish.org)
  • Autoreactive T cells specific for insulin B:11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes. (nationaljewish.org)
  • The human leukocyte antigen (HLA) system is fundamental to transplant biology. (mhmedical.com)
  • [10] It is less common in younger patients and in those with closer human leukocyte antigens (HLA) matches between donor and the patient. (wikipedia.org)
  • Cellular therapies are aimed at specific disease types and to proliferate and differentiate into the desired cell type without causing unnecessary and potentially dangerous proliferation into cancer cells or unwanted immunogenicity causing damage in surrounding tissue. (alcyomics.com)
  • The response was CD4 help-depen-dent, demonstrating the potency of H60H as a cellular antigen. (molcells.org)
  • The response induced by the H60H cellular antigen was comparable to that induced by H60 in its peak magnitude and overall immune kinetics. (molcells.org)
  • In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (β-Gal-[1→3]-α-GalNAc- O -serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. (silverchair.com)
  • The roles of antigen-specificity, responsiveness to TGFβ and APC subsets in tumour-induced expansion of regulatory T cells. (imperial.ac.uk)
  • In this brief review, a detailed account of the putative mechanisms by which the normal physiology of T cells are disturbed and why regulatory T cells fail to alleviate proinflammatory response in SLE will be discussed. (hindawi.com)
  • BALB/c splenocytes were stained with FITC Rat Anti-Mouse CD49b/Pan-NK Cells antibody (Cat. (bdbiosciences.com)
  • We targeted ovalbumin peptide exclusively to DCs in situ using an antibody to DEC-205 and studied the interaction of DCs with naive CD4(+) T cells in tolerizing or priming conditions. (ox.ac.uk)
  • The Phase 1 clinical trial, which is being conducted by researchers at Fred Hutchinson Cancer Research Center, is designed to assess the feasibility, safety, and efficacy of this novel cell therapy in the treatment of leukemia following hematopoietic stem cell transplant (HSCT). (elevate.bio)
  • Diarrhea in acute GHVD is green, mucoid, watery, and mixed with exfoliated cells forming fecal casts. (medscape.com)
  • In addition, the same principle has been found to hold for other antigenic systems, such as trinitrophenyl coupled to cells, minor histocompatibility antigens, and the H-Y model. (typeset.io)
  • The current state of clinical trials evaluating therapeutic agents which target molecules expressing on and inside T cells for the treatment of SLE will be updated. (hindawi.com)