Alien-driven diversity and alien-selected escape: a rationale for allogeneic cancer immunotherapy.

We have presented two theories relating to the function of histocompatibility antigens and their presence as alien antigens on tumor cells. The theory of alien-driven diversity suggests that the ability to effectively recognize pathogens in the form of "altered-self" derives from prior exposure to antigens cross-reactive with "altered-self" during development. Furthermore, these cross-reactive antigens are alloantigens that are expressed on autologous cells during somatic development. These somatically generated alloantigens could be the result of the same genetic alterations that produced the polymorphism of these antigens within the species. Second, the theory of alien-selected escape suggests that a tumorigenic pathogen selects a cell bearing an alien H* antigen so that the alien-infected cell is recognized as self rather than altered-self by the tumor host. We than summarized data from mouse and man consistent with these theories and with the concept that clinically evident tumors have escaped the host's immune system. Finally, we have discussed potential directions for devising immunotherapy with allogeneic cells that might circumvent the apparent unresponsiveness of the patient's immune system to his own tumor.