Oncolytic virus immunotherapy: future prospects for oncology

Abstract

Background: Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques.

Main body: The ability to deliver therapy tailored to specific cellular targets at the precise locus in which it would have its greatest impact is a profound development in anti-cancer treatment. Although immune checkpoint inhibitors have an improved tolerability profile relative to cytotoxic chemotherapy and whole beam radiation, severe immune-related adverse events have emerged as a potential limitation. These include pneumonitis, pancreatitis, and colitis, which are relatively infrequent but can limit therapeutic options for some patients. Intratumor injection of oncolytic viruses, in contrast, has a markedly lower rate of serious adverse effects and perhaps greater specificity to target tumor cells. Early stage clinical trials using oncolytic viruses show induction of effector anti-tumor immune responses and suggest that such therapies could also morph and redefine both the local target cells' niche as well as impart distant effects on remote cells with a similar molecular profile.

Conclusion: It is imperative for the modern immuno-oncologist to understand the biological processes underlying the immune dysregulation in cancer as well as the effects, uses, and limitations of oncolytic viruses. It will be with this foundational understanding that the future of oncolytic viral therapies and their delivery can be refined to forge future horizons in the direct modulation of the tumor bed.

Keywords: Cancer Immunoediting; Immunomodulatory oncolytic virus; Oncolytic viral vaccine; Oncolytic viruses; Tumor niche biology.

Fig. 1

Cancer immunoediting with three phases. In the elimination phase the antitumor effector cells and macromolecules induce apoptosis and phagocytose the immunogenic dysplastic cells. In the equilibrium phase CD8+ T cells and dendritic cells maintain a homeostasis with further mutated and less immunogenic dysplastic cells. In the escape phase the immune cells do not recognize the malignant cells. Yellow: immunogenic dysplastic cells. Gray: antitumor macromolecules. Blue: immune cells. Red-orange: sculpted dysplastic cells. Red: malignant cells

Fig. 2

a Intratumoral inoculation of an oncolytic virus with transfection and early immune cell recruitment. b Advanced transfection of an oncolytic virus into tumor and niche cells with induction of immune cells resulting in apoptosis, direct cell lysis, niche disruption, and phagocytosis. c Distant tumor immune infiltration induced by local immune conditioning. Blue: immune cells. Red: tumor cells. Orange: oncoviral particles. Green: tumor niche

Fig. 3

a Inoculation of the oncoviral vaccine with antigen detection by dendritic cells and presentation to CD4+ and CD8+ lymphocytes with clonal expansion and antibody formation. b Induction of immune storm by cytotoxic T cell invasion, antibody mediated destruction, and complement formation with feedback autophagy and apoptosis. Orange: oncoviral vaccine. Blue: immune cells. Light green: antibodies. Teal: Complement