Immuno-oncolytic viruses for the treatment of cancer

IP: Juan José Rojas Expósito, PhD

Interessos i objectius de la recerca:

Despite great progress made in the treatment of cancer, it remains one of the leading causes of death worldwide. Thus, research on novel cancer therapies is a priority. Recently, the approval of the first oncolytic virus for the treatment of human patients has refocused interest on the use of viruses as anticancer agents. Oncolytic Vaccinia viruses (VACV) are poxviruses derived from strains used worldwide in the Smallpox Eradication Program, and they are modified to selectively replicate in and destroy cancer cells. The real potential of such viruses to treat effectively cancer patients has recently become apparent in clinical trials; one reason for this recent clinical success is the realization that the antitumor immune response induced by the vector is critical for their activity. Tumor-selective viral replication leads to localized inflammation, transiently overcomes tumor-mediated immunosuppression, releases relevant tumor antigens, and helps redirecting the immune response towards tumor antigens. However, VACV strains tested to date as oncolytics focus on reaching an optimal selective replication in cancer cells, and little research has been conducted for improving their capacity to generate robust antitumor immune responses. Our group is focused on improving such capacity through an activation of an Immunogenic Cancer Cell Death (ICD) after infection. Induction of ICD has been described as key for the capacity of cancer therapeutics to activate antitumor immune responses. Two different strategies are followed for this activation:

- Study and deletion of VACV genes involved in blocking ICD activation.

- Cloning and expression of transgenes with the capacity to activate different forms of ICD.

In addition, combination of these agents with other cancer immunotherapies are also explored in order to achieve a combinatory immunotherapy with a real potential to cure solid tumors.

Research interest: Cancer, Immunotherapy, Oncolytic virus, Vaccinia virus, Immunogenic Cell Death