Vaccinia virus, a promising new therapeutic agent for pancreatic cancer

Abstract

The poor prognosis of pancreatic cancer patients signifies a need for radically new therapeutic strategies. Tumor-targeted oncolytic viruses have emerged as attractive therapeutic candidates for cancer treatment due to their inherent ability to specifically target and lyse tumor cells as well as induce antitumor effects by multiple action mechanisms. Vaccinia virus has several inherent features that make it particularly suitable for use as an oncolytic agent. In this review, we will discuss the potential of vaccinia virus in the management of pancreatic cancer in light of our increased understanding of cellular and immunological mechanisms involved in the disease process as well as our extending knowledge in the biology of vaccinia virus.

Keywords: immunotherapy; oncolytic virus; pancreatic cancer; vaccinia virus.

Figure 1.. Tumor selectivity of oncolytic viruses.

Tumor-targeted oncolytic viruses can exploit defective cellular pathways in cancer cells (top). oncolytic viruses can infect and replicate in cancer cells leading to cell lysis and release of viral particles. These in turn infect neighbor tumor cells and so forth. In normal cells (bottom) cellular defense mechanisms prevents viral replications.

Figure 2.. Multiple modes of actions of tumor-targeted oncolytic viruses.

Oncolytic viruses (OV) can kill cancer cells via a variety of mechanisms. First, they directly infect, replicate and lyse tumor cells sparing normal cells. Released virions can infect neighbor tumor cells and so forth. Second, OVs can induce immunogenic cell death associated with the release of Pathogen-associated molecular patterns and Damage-associated molecular patterns. In addition viral infection results in the release of cytokine and chemokines deviating the immune response toward a cytotoxic profile. Dendritic cells can pick tumor-associated antigens released from lysed tumor cells and prime CD8⁺ T cells to induce a tumor-specific immune response. Third, OV infection can result in vascular shutdown caused by direct viral invasion of endothelial cells and thrombosis caused by cytokine-mediated neutrophils accumulation. CD8: Cytotoxic T cell; DC: Dendritic cell; EC: Endothelial cell; N: Neutrophil; TAA: Tumor-associated antigen; TC: Tumor cell; VV: Vaccinia virus.