ArticleCancer immunology research2022
A Costimulatory CAR Improves TCR-based Cancer Immunotherapy.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- An ICAM1-Targeting Chimeric Costimulatory Receptor Mimics the Immune Synapse and Enhances Tumor-Specific T-cell Function.Cancer immunology research · 2026Article
- Advancing engineered nanoparticles for enhanced efficacy in cancer immunotherapy: optimizing nanoparticles for cancer immunotherapy.Molecular biology reports · 2026Review
- Enhancing CAR- and TCR-mediated targeting of cancer via an immune synapse-stabilizing receptor.Nature communications · 2026Article
- Review
- Current developments in T-cell receptor therapy for acute myeloid leukemia.Blood advances · 2025Review
- Cellular therapies in rheumatic and musculoskeletal diseases.Journal of translational autoimmunity · 2025Review
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Gene editing of CD3 epsilon to redirect regulatory T cells for adoptive T cell transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting of acute myeloid leukemia by five-gene engineered T cells expressing transgenic T-cell receptor specific to WT1, chimeric antigenic receptor specific to GM-CSF receptor, bispecific T-cell engager specific to CD33, and tEGFR suicide gene system.Immunotherapy advances · 2025Article
- Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.Science translational medicine · 2024Article
- Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells.Blood · 2024Article
- Chimeric antigen receptor T-cell therapy in childhood acute myeloid leukemia: how far are we from a clinical application?Haematologica · 2024Review
- Constructing co-stimulation to boost TCR therapy.Nature cancer · 2024Article
- Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies.Nature cancer · 2024Article
- Article
- Current approaches to develop "off-the-shelf" chimeric antigen receptor (CAR)-T cells for cancer treatment: a systematic review.Experimental hematology & oncology · 2023Review
- ICOS and OX40 tandem co-stimulation enhances CAR T-cell cytotoxicity and promotes T-cell persistence phenotype.Frontiers in oncology · 2023Article
- Joining Forces for Cancer Treatment: From "TCR versus CAR" to "TCR and CAR".International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
T-cell receptors (TCR) recognize intracellular and extracellular cancer antigens, allowing T cells to target many tumor antigens. To sustain proliferation and persistence, T cells require not only signaling through the TCR (signal 1), but also costimulatory (signal 2) and cytokine (signal 3) signaling. Because most cancer cells lack costimulatory molecules, TCR engagement at the tumor site results in incomplete T-cell activation and transient antitumor effects. To overcome this lack of signal 2, we genetically modified tumor-specific T cells with a costimulatory chimeric antigen receptor (CoCAR). Like classical CARs, CoCARs combine the antigen-binding domain of an antibody with costimulatory endodomains to trigger T-cell proliferation, but CoCARs lack the cytotoxic CD3ζ chain to avoid toxicity to normal tissues. We first tested a CD19-targeting CoCAR in combination with an HLA-A*02:01-restricted, survivin-specific transgenic TCR (sTCR) in serial cocultures with leukemia cells coexpressing the cognate peptide-HLA complex (signal 1) and CD19 (signal 2). The CoCAR enabled sTCR+ T cells to kill tumors over a median of four additional tumor challenges. CoCAR activity depended on CD19 but was maintained in tumors with heterogeneous CD19 expression. In a murine tumor model, sTCR+CoCAR+ T cells improved tumor control and prolonged survival compared with sTCR+ T cells. We further evaluated the CoCAR in Epstein-Barr virus-specific T cells (EBVST). CoCAR-expressing EBVSTs expanded more rapidly than nontransduced EBVSTs and delayed tumor progression in an EBV+ murine lymphoma model. Overall, we demonstrated that the CoCAR can increase the activity of T cells expressing both native and transgenic TCRs and enhance antitumor responses.
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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.