ArticleThe Journal of clinical investigation2024
Combining SiRPα decoy-coengineered T cells and antibodies augments macrophage-mediated phagocytosis of tumor cells.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Targeting the CD47-SIRPα phagocytic checkpoint in cancer: Biology, translational opportunities, and next-generation therapeutic strategies.Smart molecules : open access · 2026Review
- Engineering Oncolytic Virus-Armed Macrophages for Enhanced Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.Experimental hematology & oncology · 2026Review
- High-titer modular retroviral vectors enabled by an antisense cassette design preventing dsRNA formation during virus production.Molecular therapy. Advances · 2026Article
- Dual CD8 and TCR editing in regulatory T cells mediates HLA-A2-restricted tissue-specific homing.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Generation and Characterization of CAR-T Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Macrophages: sentinels, warriors, and healers.Human molecular genetics · 2025Review
- Gamma-retrovirus design for efficacious microRNA-mediated gene knock-down and protein co-expression without compromising titers.NAR molecular medicine · 2025Article
- Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors.Frontiers in immunology · 2025Review
- Preclinical model for evaluating human TCRs against chimeric syngeneic tumors.Journal for immunotherapy of cancer · 2024Article
- 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
Corrections and comments
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Authors and funding
10 authors.
Funding
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Abstract
The adoptive transfer of T cell receptor-engineered (TCR-engineered) T cells (ACT) targeting the HLA-A2-restricted cancer-testis epitope NY-ESO-1157-165 (A2/NY) has yielded favorable clinical responses against several cancers. Two approaches to improve ACT are TCR affinity optimization and T cell coengineering to express immunomodulatory molecules that can exploit endogenous immunity. By computational design we previously developed a panel of binding-enhanced A2/NY-TCRs including A97L, which augmented the in vitro function of gene-modified T cells as compared with WT. Here, we demonstrated higher persistence and improved tumor control by A97L-T cells. In order to harness macrophages in tumors, we further coengineered A97L-T cells to secrete a high-affinity signal regulatory protein α (SiRPα) decoy (CV1) that blocks CD47. While CV1-Fc-coengineered A97L-T cells mediated significantly better control of tumor outgrowth and survival in Winn assays, in subcutaneous xenograft models the T cells, coated by CV1-Fc, were depleted. Importantly, there was no phagocytosis of CV1 monomer-coengineered T cells by human macrophages. Moreover, avelumab and cetuximab enhanced macrophage-mediated phagocytosis of tumor cells in vitro in the presence of CV1 and improved tumor control upon coadministration with A97L-T cells. Taken together, our study indicates important clinical promise for harnessing macrophages by combining CV1-coengineered TCR-T cells with targeted antibodies to direct phagocytosis against tumor cells.
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