Dr Chmielowski on the Rationale for Investigating Oncolytic Viruses in Melanoma

“The story of oncolytic viruses is not completely new. For years, people knew herpes-based viruses could proliferate in the tumor environment. [Through this], they can destroy a local tumor, which leads to local inflammation, cytokine release, and possible release of tumor antigens. This will lead to enhanced immune responses.”

Bartosz Chmielowski, MD, PhD, health sciences clinical professor, medicine, Division of Hematology-Oncology, Sarcoma and Connective Tissue Medical Oncology, UCLA Health, discusses the rationale for investigating oncolytic viruses in melanoma.

Although the concept of oncolytic viruses is not entirely new, it represents an evolving approach in cancer therapy, Chmielowski begins. One oncolytic virus, talimogene laherparepvec (T-VEC; Imylgic), has been FDA approved for the treatment of patients with advanced melanoma since 2015. T-VEC is administered via direct intratumoral injection, making it most suitable for patients with accessible lesions, such as those on the skin, in subcutaneous nodules, or within local lymph nodes, Chmielowski explains.

T-VEC is based on a modified herpes simplex virus designed to replicate selectively within the tumor microenvironment, Chmielowski details. Viral proliferation in tumor cells leads to localized tumor destruction, which in turn stimulates an inflammatory response, he says. This inflammation is characterized by cytokine release and, potentially, the release of tumor-associated antigens, which can enhance systemic antitumor immune responses, according to Chmielowski.

A common question arises regarding the efficacy of such oncolytic virus treatments in addressing uninjected lesions, which reflects the core challenge of achieving a systemic therapeutic effect from localized injections, Chmielowski continues. The therapeutic goal is to induce an immune-mediated response that extends beyond the injected sites, enabling control of distant metastases, he notes.

The potential of oncolytic viruses lies in their ability to combine direct oncolysis with immune activation, Chmielowski states. However, achieving consistent systemic efficacy remains a critical focus of ongoing research, he says. Investigators are exploring combinations with immune checkpoint inhibitors and other modalities to enhance systemic responses and broaden the applicability of oncolytic virus therapy in oncology, Chmielowski concludes.