Researchers led by Ludwig Stanford’s Ravi Majeti reported in a March publication in Cancer Discovery that they had reprogrammed cancer cells isolated from mouse models of four types of cancer into potent anti-tumor vaccines. Ravi’s lab has previously shown that the cells of a type of leukemia can be reprogrammed to resemble macrophages, which are professional antigen presenting cells (APCs). The reprogrammed cancer cells retain genomic aberrations of their cancerous progenitors but are not malignant. Ravi and colleagues showed in this study that these “tumor-reprogrammed APCs” (or TR-APCs) can, like macrophages, present a broad spectrum of the cancer antigens encoded in their genomes to T cells, directing a concerted assault on cancerous cells. Use of the TR-APCs in a mouse model of leukemia potently activated helper T cells that orchestrate adaptive immune responses and killer T cells that destroy sick and cancerous cells, eradicating disease in the mice. Like living vaccines, the reprogrammed cells also instilled in the mice a memory of the cancer, prompting them to reject subsequent attempts to engraft the same cancer. The TR-APC vaccines also extended survival in mouse models of solid tumors, namely fibrosarcoma and breast and bone cancer. Ravi and his team demonstrated that TR-APCs derived from leukemia patients could activate T cells taken from those same patients in cell cultures, suggesting the approach might be ripe for translational development.
Reprogramming cancer into antigen-presenting cells as a novel immunotherapy
Cancer Discovery, 2023 March 1