Engineered tumor cell-derived vaccines against cancer: The art of combating poison with poison

Tumor vaccination is a promising approach for tumor immunotherapy because it presents high specificity and few side effects. However, tumor vaccines that contain only a single tumor antigen can allow immune system evasion by tumor variants. Tumor antigens are complex and heterogeneous, and identifying a single antigen that is uniformly expressed by tumor cells is challenging. Whole tumor cells can produce comprehensive antigens that trigger extensive tumor-specific immune responses. Therefore, tumor cells are an ideal source of antigens for tumor vaccines. A better understanding of tumor cell-derived vaccines and their characteristics, along with the development of new technologies for antigen delivery, can help improve vaccine design. In this review, we summarize the recent advances in tumor cell-derived vaccines in cancer immunotherapy and highlight the different types of engineered approaches, mechanisms, administration methods, and future perspectives. We discuss tumor cell-derived vaccines, including whole tumor cell components, extracellular vesicles, and cell membrane-encapsulated nanoparticles. Tumor cell-derived vaccines contain multiple tumor antigens and can induce extensive and potent tumor immune responses. However, they should be engineered to overcome limitations such as insufficient immunogenicity and weak targeting. The genetic and chemical engineering of tumor cell-derived vaccines can greatly enhance their targeting, intelligence, and functionality, thereby realizing stronger tumor immunotherapy effects. Further advances in materials science, biomedicine, and oncology can facilitate the clinical translation of tumor cell-derived vaccines.