Repurposing Tumor Cells: A Paradigm Shift in Cell-Based Therapies for Cancer.

Conventional cancer therapies emphasize eradication, often at the expense of harming healthy tissue and causing immune compromise. This article explores a paradigm-shifting concept: repurposing tumor cells not merely as targets but as active therapeutic agents. By harnessing their self-homing ability, antigen diversity, and adaptive survival mechanisms, these engineered tumor cells can be repurposed to deliver therapeutic payloads, remodel the tumor microenvironment, and even function as antigen-presenting cells (APC). We begin by critically analyzing the mechanistic failures of early whole-cell vaccine approaches, highlighting how their limited efficacy stemmed from underestimating both the tumor's potent adaptive resistance and the deeply immunosuppressive nature of its microenvironment. We then discuss next-generation strategies designed to overcome these hurdles, with approaches ranging from "killer vaccines" and APC-like reprogramming to Trojan horse delivery of oncolytic viruses. The translational challenges, ranging from multilayered safety engineering, GMP manufacturing, regulatory navigation, patient selection, to ethical considerations, are examined in depth, with key insights drawn from the clinical evolution of chimeric antigen receptor T-cell therapy. We conclude by outlining a clinical roadmap and rational combinatorial strategies, proposing that if these barriers are overcome, tumor cell-based therapies could emerge as complements to immune checkpoint inhibitors and adoptive cell therapies, thus transforming the tumor from an adversary into a catalyst of its own defeat.