viroimmunotherapy

Viroimmunotherapy is a therapeutic approach that combines virotherapy with immunotherapy to treat cancer by using viruses to infect and kill tumor cells while also stimulating an anti-tumor immune response. The field includes oncolytic virotherapy, in which replication-competent viruses preferentially replicate in cancer cells, and the use of viral vectors engineered to deliver immunostimulatory molecules or tumor antigens. The goal is to achieve direct tumor lysis and to convert the tumor into an in situ vaccine that trains the immune system to recognize and attack malignant cells.

Mechanisms of action include selective oncolysis, release of tumor-associated antigens, and activation of innate immune pathways such as interferon signaling. The ensuing dendritic cell maturation and T cell priming can generate systemic, tumor-specific immune responses. Some viruses are engineered to express cytokines or co-stimulatory molecules to enhance immunity. In clinical development, viroimmunotherapy is often used in combination with other immunotherapies, such as immune checkpoint inhibitors, to overcome resistance and broaden anti-tumor activity. Notable examples include talimogene laherparepvec (T-VEC), a modified herpes simplex virus that expresses GM-CSF and is approved for melanoma; other virus platforms, including reovirus, vaccinia, adenovirus, and measles viruses, are active in various phases of development.

Challenges for viroimmunotherapy include managing safety and inflammatory responses, overcoming pre-existing antiviral immunity, achieving effective delivery to tumors, and manufacturing complexity. Delivery methods range from intratumoral injections to systemic administration, with research aimed at enhancing tumor targeting and minimizing off-target effects. As a modality, viroimmunotherapy is being explored as a component of combination regimens and broadening the landscape of cancer immunotherapy.