Preexisting immunity: Barrier or bridge to effective oncolytic virus therapy?

Oncolytic viruses (OVs) represent a highly promising treatment strategy for a wide range of cancers, by mediating both the direct killing of tumor cells as well as mobilization of antitumor immune responses. As many OVs circulate in the human population, preexisting OV-specific immune responses are prevalent. Indeed, neutralizing antibodies (NAbs) are abundantly present in the human population for commonly used OVs, such as Adenovirus type 5 (Ad5), Herpes Simplex Virus-1 (HSV-1), Vaccinia virus, Measles virus, and Reovirus. This review discusses (pre)clinical evidence regarding the effect of preexisting immunity against OVs on two distinct aspects of OV therapy; OV infection and spread, as well as the immune response induced upon OV therapy. Combined, this review provides evidence that consideration of preexisting immunity is crucial in realizing the full potential of the highly promising therapeutic implementation of OVs. Future investigation of current gaps in knowledge highlighted in this review should yield a more complete understanding of this topic, ultimately allowing for better and more personalized OV therapies.