Viral Oncolysates as Human Tumor Vaccines

Abstract

Postoncolytic immunity entails immune reactions acquired through an oncolytic virus infection or through repeated immunizations with viral oncolysates (or virally modified tumor cell membranes) that are valid and operational also against virally not modified tumor cells of the same type. NK cells react to budding virions, induce target cell lysis primarily but not exclusively by the production of granzymes and pore-forming proteins and operate without direction from memory cells. In contrast, immune T cells (including some TIL) are MHC-restricted, act under the direction of memory cells and lyse target cells primarily but not exclusively by the release of lymphotoxin (TNFβ) causing programmed cell death (apoptosis) through endonuclease activation and target cell DNA fragmentation. This author proposes that it is not NK, but the immune T cells that mediate postoncolytic immunity. Oncogene amplification may protect immortalized tumor cells even when expressing peptide antigens through MHC molecules against lymphotoxin-mediated apoptosis; but virally-infected tumor cells releasing budding virions remain susceptible to NK cells. Highly immunogenic viral oncolysates should present both budding virions for NK cells and processed viral and tumoral peptide antigens co-jointly for immune T cells.

Key Words:

• oncolytic viruses
• viral oncolysates
• natural killer cells
• immune T cells
• programmed cell death (apoptosis)
• postoncolytic immunity
• pore-forming proteins
• lymphotoxin (TNFβ)