ArticleThe Journal of clinical investigation2010
MHC-restricted fratricide of human lymphocytes expressing survivin-specific transgenic T cell receptors.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 87 citations in OpenAlex.
- Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors.Cancer immunology, immunotherapy : CII · 2014Trial
- Current developments in T-cell receptor therapy for acute myeloid leukemia.Blood advances · 2025Review
- Immunopeptidomics identified antigens for mRNA-lipid nanoparticle vaccines with alpha-galactosylceramide in multiple myeloma therapy.Journal for immunotherapy of cancer · 2025Article
- Chimeric antigen receptor-induced antigen loss protects CD5.CART cells from fratricide without compromising on-target cytotoxicity.Cell reports. Medicine · 2024Article
- Advances in CAR-T-cell therapy in T-cell malignancies.Journal of hematology & oncology · 2024Review
- Genome Editing for Engineering the Next Generation of Advanced Immune Cell Therapies.Advances in experimental medicine and biology · 2023Article
- Evolution by innovation as a driving force to improve TCR-T therapies.Frontiers in oncology · 2023Review
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- CAR-T cell development for Cutaneous T cell Lymphoma: current limitations and potential treatment strategies.Frontiers in immunology · 2022Review
- Article
- Development of a CD8 co-receptor independent T-cell receptor specific for tumor-associated antigen MAGE-A4 for next generation T-cell-based immunotherapy.Journal for immunotherapy of cancer · 2021Article
- Novel targeted therapies of T cell lymphomas.Journal of hematology & oncology · 2020Review
- Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease.Molecular therapy. Methods & clinical development · 2020Review
- Hematopoietic Cell Transplantation and Adoptive Cell Therapy in Peripheral T Cell Lymphoma.Current hematologic malignancy reports · 2020Review
- DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing.EBioMedicine · 2020Article
- Novel Survivin Peptides Screened With Computer Algorithm Induce Cytotoxic T Lymphocytes With Higher Cytotoxic Efficiency to Cancer Cells.Frontiers in molecular biosciences · 2020Article
- A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Overcoming Target Driven Fratricide for T Cell Therapy.Frontiers in immunology · 2018Article
- Tools to define the melanoma-associated immunopeptidome.Immunology · 2017Review
- A Dynamic Model of Immune Responses to Antigen Presentation Predicts Different Regions of Tumor or Pathogen Elimination.Cell systems · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apoptosis inhibitor protein survivin is overexpressed in many tumors, making it a candidate target molecule for various forms of immunotherapy. To explore survivin as a target antigen for adoptive T cell therapy using lymphocytes expressing survivin-specific transgenic T cell receptors (Tg-TCRs), we isolated HLA-A2-allorestricted survivin-specific T cells with high functional avidity. Lymphocytes expressing Tg-TCRs were derived from these T cells and specifically recognized HLA-A2+ survivin+ tumor cells. Surprisingly, HLA-A2+ but not HLA-A2- lymphocytes expressing Tg-TCRs underwent extensive apoptosis over time. This demise was caused by HLA-A2-restricted fratricide that occurred due to survivin expression in lymphocytes, which created ligands for Tg-TCR recognition. Therefore, survivin-specific TCR gene therapy would be limited to application in HLA-A2-mismatched stem cell transplantation. We also noted that lymphocytes that expressed survivin-specific Tg-TCRs killed T cell clones of various specificities derived from HLA-A2+ but not HLA-A2- donors. These results raise a general question regarding the development of cancer vaccines that target proteins that are also expressed in activated lymphocytes, since induction of high-avidity T cells that expand in lymph nodes following vaccination or later accumulate at tumor sites might limit themselves by self-MHC-restricted fratricide while at the same time inadvertently eliminating neighboring T cells of other specificities.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.