A Novel Strategy For Tumor Therapy Combining Cell Apoptosis And Active Immunity Induced By Caspy2, A Zebrafish Caspase

Caspy2, a zebrafish protease containing N-terminal pyrin domains, is an active caspase for inducing apoptosis in mammalian cells. In the present study, we reported that expression of caspy2 induced apoptosis in tumor cells and the remnants of apoptotic cells were modified by peptides derived from the foreign antigen. Through the modification, anti-tumor immunity for MethA and CT26 tumor was elicited in immune-competent murine models. Infiltration of lymphocytes was observed apparently in tumor tissues. Meanwhile, the local production of modified apoptotic cell remnants can mediate a "distant bystander" effect. The adoptive transfer of CD4⁺ or CD8⁺ T lymphocytes showed anti-tumor activities. In vivo depletion of CD8⁺ T lymphocytes nearly completed to abrogate caspy2's anti-tumor activity, whereas the depletion of CD4⁺ cells showed partial abrogation. MHC class I-dependent CD8⁺ CTL activity was found with ⁵¹Cr release assay. In this study, we developed a novel anticancer strategy that combines both induction of apoptosis and immune response in mice bearing tumors with caspy2, showing that there is a significant delay in tumor growth and prolongation of life span in immune-competent mice. This approach may provide an important way for treatment of cancer.