Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer

Abstract

Oncolytic immunotherapy is a research area of cancer immunotherapy investigating the use of modified viruses to target cancer cells. A variety of different viral backbones (e.g., adenovirus, reovirus) with a diverse range of genetic modifications are currently being investigated for the treatment of a variety of cancers. The oncolytic virus that has advanced the furthest in clinical development is talimogene laherparepvec, a recombinant HSV-1 virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF). In a phase 3 study in patients with unresectable metastatic melanoma, intralesional talimogene laherparepvec treatment resulted in a higher durable response rate compared with subcutaneous GM-CSF treatment (16.3 versus 2.1%; P < 0.001). Notably, responses were observed at uninjected lesions including visceral lesions, indicating a systemic antitumor response had occurred. Studies evaluating combination treatments involving oncolytic viruses and immunologic agents are ongoing. This review focuses on the mechanisms of action for oncolytic viruses and highlights select agents and combinations currently in development.

Correlates of response and outcomes with talimogene laherperpvec

“…Oncolytic viruses are naturally occurring or engineered viruses, which selectively replicate and kill malignant cells and can induce systemic antitumor immune responses. 5,6 Although the therapeutic potential for oncolytic viruses has been recognized for decades, they were only recently introduced into the clinical setting. 5 Talimogene laherparepvec (TVEC) is a herpes simplex virus-1-based oncolytic virus demonstrated to have potent antitumor effects against melanoma.…”

Development of oncolytic virotherapy: from genetic modification to combination therapy

“…OVs can kill tumor cells through the following mechanisms: selectively replicating in tumor cells and causing the oncolysis of tumor cells [121]; inducing the immunogenic cell death of tumor cells, thereby releasing damageassociated molecular pattern molecules, tumor-associated antigens, and pathogen-associated molecule patterns that stimulate antitumor immunity to kill other tumor cells [91]; and destroying tumor vasculature to indirectly kill tumor cells [122,123]. Insertion of genes coding for immunostimulatory molecules/cytokines, suicide genes, ECMdegrading enzymes, and anti-vasculature molecules can improve the antitumor efficacy of OVs [76,124,125].…”

Designer Oncolytic Adenovirus: Coming of Age

“…The This outcome is unlikely to be so clear cut in an immune competent model given the immune stimulatory effects, which are now accepted as a primary mode of action for oncolytic viruses, are likely to activate a T-cell responses against neighbouring cancer cells [239][240][241][242][243] . Yet it is a reminder of the danger of monotargeted therapies, something which has been considered in proof of concept experiments using two affibodies inserted into the Fiber HI-loop with different tropism to create a virus with dual specificity 244 .…”