Solid tumor rejection using personalized incompatible human leukocyte antigen (HLA) and blood group ABH antigens

Cancer immunotherapies have become mainstream, targeting tumor elimination via various mechanisms, albeit with varied effectiveness. Here, we review briefly the current landscape of cancer immunotherapies and the central role of human leukocyte antigen (HLA) in them. We then propose a new kind of immunotherapy for solid tumors, where the key is the involvement of antigens and antibodies unrelated to the tumor itself. In this approach, we consider the tumor as akin to a transplanted organ, which can be rejected by two different mechanisms of incompatibility. The first involves the intra-tumor administration of mRNA blueprints of incompatible (to the patient) HLA proteins, leading to their synthesis and, hopefully, elicitation of an anti-tumor immune reaction, assuming immunocompetency. The second therapy involves the direct, intra-tumor administration of anti-A/B/H blood group antibodies lining the blood and lymph vessels of the tumor. In organ transplantation, AB incompatibility leads to organ rejection, and the same effect would be expected when anti-A/B/H antibodies (depending on the patient's ABO group) are injected into the tumor. Notably, the anti-tumor effect by the preformed anti-blood group antibodies is complement-mediated and should not be affected by tumor immunoevasion. This proposed cancer immunotherapy aimed at promoting tumor rejection via antigen incompatibility offers a novel cancer treatment approach that warrants further investigation.