ArticleScience translational medicine2021
TCR β chain-directed bispecific antibodies for the treatment of T cell cancers.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 53 citations in OpenAlex.
- From molecular pathogenesis to novel Therapeutic approaches - a review of recent advances in the treatment of peripheral T cell Lymphomas.Biomarker research · 2026Review
- TCRVβ-targeting antibody-drug conjugates as a novel strategy to eliminate malignant T cells in T cell cancers.Blood advances · 2026Article
- Spatial Regulation of CAR Signaling Enables Logic-Gated Activity.bioRxiv : the preprint server for biology · 2026Article
- IGLV3-21Haematologica · 2026Article
- Cellular and molecular aberrations generating new immunotherapeutic approaches in mycosis fungoides and Sézary syndrome: a comprehensive review of literature.Frontiers in immunology · 2026Review
- TRBC2-targeting antibody-drug conjugates for the treatment of T cell cancers.Nature cancer · 2025Article
- Personalized Immunotherapy for T Cell Lymphomas: From Immune Escape to Precision Therapeutics.Journal of personalized medicine · 2025Review
- Antibody Matrimony in a Duel of Hearts.JACC. Basic to translational science · 2025Article
- EpicPred: predicting phenotypes driven by epitope-binding TCRs using attention-based multiple instance learning.Bioinformatics (Oxford, England) · 2025Article
- T-cell receptor architecture and clonal tiding provide insight into the transformation trajectory of peripheral T-cell lymphomas.Haematologica · 2025Article
- Six events that shaped antibody approvals in oncology.Frontiers in immunology · 2025Review
- Engaging T cells for cleanup.Frontiers in immunology · 2025Review
- Targeting CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model.Frontiers in immunology · 2025Article
- Antibody-Based Therapies for Peripheral T-Cell Lymphoma.Cancers · 2024Review
- All-in-one Hangzhou Protocol: killing four birds with one stone.Cell research · 2024Article
- T cell receptor-directed antibody-drug conjugates for the treatment of T cell-derived cancers.Molecular therapy. Oncology · 2024Article
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- TCRvβ8 chimeric antigen receptor natural killer cells exhibit potent preclinical activity against T-cell malignancies.Clinical and translational medicine · 2024Article
- Selective targeting of malignant T cells.Nature cancer · 2024Article
- Cancer therapy with antibodies.Nature reviews. Cancer · 2024Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Immunotherapies such as chimeric antigen receptor (CAR) T cells and bispecific antibodies redirect healthy T cells to kill cancer cells expressing the target antigen. The pan-B cell antigen-targeting immunotherapies have been remarkably successful in treating B cell malignancies. Such therapies also result in the near-complete loss of healthy B cells, but this depletion is well tolerated by patients. Although analogous targeting of pan-T cell markers could, in theory, help control T cell cancers, the concomitant healthy T cell depletion would result in severe and unacceptable immunosuppression. Thus, therapies directed against T cell cancers require more selective targeting. Here, we describe an approach to target T cell cancers through T cell receptor (TCR) antigens. Each T cell, normal or malignant, expresses a unique TCR β chain generated from 1 of 30 TCR β chain variable gene families (TRBV1 to TRBV30). We hypothesized that bispecific antibodies targeting a single TRBV family member expressed in malignant T cells could promote killing of these cancer cells, while preserving healthy T cells that express any of the other 29 possible TRBV family members. We addressed this hypothesis by demonstrating that bispecific antibodies targeting TRBV5-5 (α-V5) or TRBV12 (α-V12) specifically lyse relevant malignant T cell lines and patient-derived T cell leukemias in vitro. Treatment with these antibodies also resulted in major tumor regressions in mouse models of human T cell cancers. This approach provides an off-the-shelf, T cell cancer selective targeting approach that preserves enough healthy T cells to maintain cellular immunity.
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Registered trials
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.