ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Bispecific Antibodies Enable Synthetic Agonistic Receptor-Transduced T Cells for Tumor Immunotherapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Modular (universal) CAR-T platformsFrontiers in immunology · 2024Pooled it
- Evolution of bispecific and multispecific antibodies in cancer therapy.The Lancet regional health. Europe · 2026Review
- NR2F6 deletion revives CAR-T cell function and induces antigen-agnostic immune memory in solid tumors.Nature communications · 2026Article
- RIG-I agonists promote antigen-spreading and facilitate durable CAR-T responses in pancreatic ductal adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Mechanism of Bispecific Antibodies and Clinical Research Advances in Lung Cancer.Current cancer drug targets · 2026Review
- The Current Landscape of Modular CAR T Cells.International journal of molecular sciences · 2025Review
- Innovative gene engineering strategies to address tumor antigen escape in cell therapy.Journal of translational medicine · 2025Review
- The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer.Journal of advanced research · 2025Review
- PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis.Cancer immunology, immunotherapy : CII · 2024Article
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Mutation-specific CAR T cells as precision therapy for IGLV3-21Nature communications · 2024Article
- Universal CAR 2.0 to overcome current limitations in CAR therapy.Frontiers in immunology · 2024Review
- Fully equipped CARs to address tumor heterogeneity, enhance safety, and improve the functionality of cellular immunotherapies.Frontiers in immunology · 2024Review
- Programmable multispecific DNA-origami-based T-cell engagers.Nature nanotechnology · 2023Article
- Engineering enhanced chimeric antigen receptor-T cell therapy for solid tumors.Immuno-oncology technology · 2023Review
- Bispecific antibodies redirect synthetic agonistic receptor modified T cells against melanoma.Journal for immunotherapy of cancer · 2023Article
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
- Immunotargeting of Cancer Stem Cells.Cancers · 2023Review
- CD123 a Therapeutic Target for Acute Myeloid Leukemia and Blastic Plasmocytoid Dendritic Neoplasm.International journal of molecular sciences · 2023Review
- Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
Abstract
purposeGenetically engineered T cells are powerful anticancer treatments but are limited by safety and specificity issues. We herein describe an MHC-unrestricted modular platform combining autologous T cells, transduced with a targetable synthetic agonistic receptor (SAR), with bispecific antibodies (BiAb) that specifically recruit and activate T cells for tumor killing. EXPERIMENTAL
designBiAbs of different formats were generated by recombinant expression. T cells were retrovirally transduced with SARs. T-cell activation, proliferation, differentiation, and T-cell-induced lysis were characterized in three murine and human tumor models
resultsMurine T cells transduced with SAR composed of an extracellular domain EGFRvIII fused to CD28 and CD3ζ signaling domains could be specifically recruited toward murine tumor cells expressing EpCAM by anti-EGFRvIII × anti-EpCAM BiAb. BiAb induced selective antigen-dependent activation, proliferation of SAR T cells, and redirected tumor cell lysis. Selectivity was dependent on the monovalency of the antibody for EGFRvIII. We identified FAS ligand as a major mediator of killing utilized by the T cells. Similarly, human SAR T cells could be specifically redirected toward mesothelin-expressing human pancreatic cancer cells.
conclusionsWe describe a novel ACT platform with antitumor activity in murine and human tumor models with a distinct mode of action that combines adoptive T-cell therapy with bispecific antibodies.
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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.