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- W4247924043 abstract "Treatment of advanced, poorly immunogenic tumors in animal models, considered the closest simulation available thus far for conditions observed in cancer patients, remains a major challenge for cancer immunotherapy. We reported previously that established tumors in mice receiving an agonistic mAb to the T cell costimulatory molecule 4-1BB (CD137) regress due to enhanced tumor antigen–specific cytotoxic T lymphocyte responses. In this study, we demonstrate that several poorly immunogenic tumors, including C3 tumor, TC-1 lung carcinoma, and B16-F10 melanoma, once established as solid tumors or metastases, are refractory to treatment by anti–4-1BB mAb. We provide evidence that immunological ignorance, rather than anergy or deletion, of tumor antigen–specific CTLs during the progressive growth of tumors prevents costimulation by anti–4-1BB mAb. Breaking CTL ignorance by immunization with a tumor antigen–derived peptide, although insufficient to stimulate a curative CTL response, is necessary for anti–4-1BB mAb to induce a CTL response leading to the regression of established tumors. Our results suggest a new approach for immunotherapy of human cancers." @default.
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- W4247924043 date "2002-03-01" @default.
- W4247924043 modified "2023-10-18" @default.
- W4247924043 title "Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors" @default.
- W4247924043 doi "https://doi.org/10.1172/jci200214184" @default.
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