Whole Tumor Cells and Their Derivatives for the Development of Therapeutic Cancer Vaccines

One approach to therapeutic cancer vaccine development uses whole tumor cells or their lysates as sources of a broad repertoire of tumor antigens. A key advantage of this strategy is that it does not require prior identification of tumor antigens, unlike personalized neoantigen peptide or mRNA vaccines, potentially reducing the time and cost of vaccine development. However, late-phase clinical trials have not demonstrated sufficient efficacy of tumor cell-based cancer vaccines. Currently, strategies to enhance the therapeutic potential of vaccines based on whole tumor cells and their derived lysates are being actively developed, and the vaccine potential of individual tumor cell components, such as cell membranes and extracellular vesicles, is under investigation. In this review, we systematize data on how whole tumor cells and their derivatives (lysates, cell membranes, and extracellular vesicles) are used to generate therapeutic cancer vaccines, analyze the results of experimental and clinical studies, and evaluate promising engineering and combination therapy strategies capable of overcoming the current limitations of this platform.