
Adoptive immunotherapy with antigen-specific T cells has shown promise for the treatment of malignancies. However, infused T cells are unable to redirect resident T cells, limiting potential benefit. While the infusion of bispecific T-cell engagers can redirect resident T cells to tumors, these molecules have a short half-life, and do not self amplify. To overcome these limitations, we generated T cells expressing a secretable T-cell engager specific for CD3 and EphA2, an antigen expressed on a broad range of human tumors (EphA2-ENG T cells). EphA2-ENG T cells were activated and recognized tumor cells in an antigen-dependent manner, redirected bystander T cells to tumor cells, and had potent antitumor activity in glioma and lung cancer severe combined immunodeficiency (SCID) xenograft models associated with a significant survival benefit. This new class of tumor-specific T cells, with the unique ability to redirect bystander T cells, may be a promising alternative to current immunotherapies for cancer.
Male, Lung Neoplasms, CD3 Complex, T-Lymphocytes, Genetic Vectors, Gene Expression, Mice, SCID, Immunotherapy, Adoptive, Mice, Antigens, Neoplasm, Cell Line, Tumor, Drug Discovery, Genetics, Animals, Humans, Molecular Biology, Pharmacology, Mice, Inbred ICR, Brain Neoplasms, Receptor, EphA2, Bystander Effect, Glioma, Survival Analysis, Retroviridae, Molecular Medicine
Male, Lung Neoplasms, CD3 Complex, T-Lymphocytes, Genetic Vectors, Gene Expression, Mice, SCID, Immunotherapy, Adoptive, Mice, Antigens, Neoplasm, Cell Line, Tumor, Drug Discovery, Genetics, Animals, Humans, Molecular Biology, Pharmacology, Mice, Inbred ICR, Brain Neoplasms, Receptor, EphA2, Bystander Effect, Glioma, Survival Analysis, Retroviridae, Molecular Medicine
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