Advances and Challenges in Pluripotent Stem Cell‐Based Whole‐Cell Vaccines for Cancer Treatment

In recent decades, an unexpected application of pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), as a novel source for whole‐cell vaccines (WCVs) against cancer has attracted attention in the field of tumor immunotherapy. WCVs utilize entire cells as a source of antigens capable of activating various immune responses, including both cellular and humoral immunity. Traditional WCVs typically employ inactivated or genetically modified tumor cells to stimulate the immune system and induce tumor‐specific immune responses. Since we first reported in 2009, it has been gradually recognized that the immunogenicity and multi‐target potential of PSCs make them an ideal vaccine platform. Although WCVs are still associated with challenges such as ethical concerns, poor immunogenicity, and insufficient immune stimulation, it has become clear that PSC‐based anticancer vaccines contain tumor‐associated antigens. These vaccines can be delivered in various forms, including cell membrane fusion, stem cell outer membrane vesicles (OMVs), and cryopreserved whole‐cell vaccines. Our review aims to summarize the history and status of PSC vaccines, including adjuvant selection, cell‐free vaccines, and mechanisms of action for PSC vaccines. We also discuss challenges and perspectives in this line of research.