Allogenic naïve and primed embryonic stem cells elicit a cancer-specific immunotherapeutic response in C57Bl6 mice

Stem cells are emerging sources of antigens for cancer immunotherapy. Here, we demonstrated the capacity of TNG-A mouse embryonic stem cells to guide the immune system against tumors derived from E0771 mouse breast cancer cells. TNG-A cells were cultured either in the presence or absence of inhibitors of the mitogen-activated protein kinase kinase 1 and 2 and the glycogen synthase kinase-3 beta (+2i and -2i, respectively). While the presence of 2i preserves TNG-A pluripotency, 2i removal altered the morphology, transcriptome, and proteome of TNG-A cells, increasing their phenotypic similarities with E0771 cancer cells. Double immunization with TNG-A cells (cultured in the presence or absence of 2i) followed by E0771 implantation, drastically decreased E0771-derived tumor growth in mice. Serum cytokine quantifications indicated a transient immune reaction associated with tumor regression. Nevertheless, E0771 implantation followed by TNG-A immunization, or immunization with TNG-A cells impaired for tight junction proteins such as Claudin 6, failed to combat tumor growth. Our findings demonstrate the anti-tumor effects of embryonic stem cells and anticipate their potential as an allogenic source for cancer immunotherapy.