Neoadjuvant Oncolytic Virus Therapy in a Murine Model of Cancer Surgery

Abstract

Surgery is the primary treatment modality for most solid tumours. Despite complete resection, the development of metastatic disease limits it curative potential and provides the rationale for neoadjuvant (preoperative) therapies. Oncolytic Viruses (OVs) are replicating therapeutics that are selected or engineered to grow in malignant cell types and are capable of killing the infected target cell, while leaving normal, adjacent cells unharmed. OVs may be an ideal candidate for generating a potent anti-tumour immune response due to effective recruitment of immune cells into the tumour microenvironment, proper activation of immune cells, and generation of tumour antigen-specific T cells. Preoperative OV therapy may serve as a neoadjuvant immunotherapy capable of preventing the development of metastatic disease by generating an effective immune response. Although VSVDelta51GM-CSF treatment of CT26lacZ tumours is able to generate an anti-tumour immune response capable of preventing the growth of a subsequent CT26lacZ tumour, preoperative VSVDelta51GM-CSF treatment of primary tumours in a CT26lacZ surgery model was unable to generate an immune response capable of rejecting a secondary tumour. This abrogation of protection against the secondary CT26lacZ tumour was observed to be a result of the surgical intervention. Preoperative VSVDelta51GM-CSF and VSVDelta51 treatment IV of primary tumours in a B16-F10 surgery model was unable to generate an immune response capable of reducing the number of secondary surface lung metastases. JXS94mGMCSF treatment IT of a primary tumour in a B16-F10 surgery model was able to reduce the number of secondary surface lung metastases, while JXS94mGMCSF injected IV was not. This suggests that one of the factors in the induction of an anti-tumour immune response by neoadjuvant therapy in a surgical model may be the route of administration of ov.