Enhanced therapeutic effect using sequential administration of antigenically distinct oncolytic viruses expressing oncostatin M in a Syrian hamster orthotopic pancreatic cancer model

摘要

The limited efficacy of current treatments against pancreatic cancer has prompted the search of newalternatives such as virotherapy. Activation of the immune response against cancer cells is emerging as one of themain mechanisms of action of oncolytic viruses (OV). Direct oncolysis releases tumor antigens, and viral replicationwithin the tumor microenvironment is a potent danger signal. Arming OV with immunostimulatory transgenesfurther enhances their therapeutic effect. However, standard virotherapy protocols do not take full advantage of OVas cancer vaccines because repeated viral administrations may polarize immune responses against strong viralantigens, and the rapid onset of neutralizing antibodies limits the efficacy of redosing. An alternative paradigmbased on sequential combination of antigenically distinct OV has been recently proposed.