A novel biosynthesized vaccine based on tumor cells for peritoneal metastasis treatment in colon cancer

Inspired by the application of organisms as bioreactors in developing drug delivery systems, the living organisms that have undergone biosynthesis are expected to further expand their application scenarios in biomedical domain. Herein, a whole tumor cell vaccine, named as Au@Cell, was developed by harnessing tumor cells as bioreactors to achieve the reduction of chloroauric acid in a mild aqueous phase system within 24 h. The biogeneration process in tumor cells enabled the retention of plenary tumor antigens, enhancement of MHC-I molecules, and generation of innate immune agonist (dsRNA), demonstrating potential for application as a therapeutic cancer vaccine. The resulting cancer vaccine was proved to be non-tumorigenic, revealing favorable in vivo safety. When administrated via intraperitoneal injection, Au@Cell achieved dual-targeting effects on both spleen and peritoneal tumors. Moreover, the combination therapy of Au@Cell and an immune checkpoint inhibitor (αPD-L1) could reprogram the tumor microenvironment by activating CD8+ T cells and effector B lymphocytes, exhibiting favorable anti-tumor effect in MC38 peritoneal carcinomatosis. This study suggested an alternative vaccine manufacturing strategy enabled by the biogeneration process in tumor cells to augment the efficacy against colon cancer-related peritoneal carcinomatosis.