Cancer immunotherapy with oncolytic myxoma virus

Viruses have been developed as oncolytic immunotherapy agents due to their ability to target and kill cancer cells while sparing normal cells. Additionally, engineered oncolytic viruses (OVs) can alter the immunosuppressive tumor microenvironment, making other cancer therapies more favorable. Many candidate OVs are currently in clinical trials as monotherapy or in combination with other cancer therapeutics. Oncolytic myxoma virus (MYXV), a member of the Poxviridae family that infects only leporids in nature and causes no infection to humans or other animals, has been developed as an oncolytic immunotherapy agent. MYXV selectively infects cancer cells due to the accumulation of mutations and the absence of functional antiviral responses within these cells. The large dsDNA genome of MYXV is amenable to the deletion of non-essential immunomodulatory genes and to the insertion of multiple immunostimulatory transgenes with antitumor properties. The systemic and local administration of engineered MYXV promotes changes within the tumor microenvironment that reverse immunosuppression and improve immune activation and infiltration. These cancer tropism and immune activation properties, combined with the absence of preexisting antibodies, led to the testing of MYXV in various types of preclinical cancer models, including pancreatic cancer, glioblastoma, ovarian cancer, melanoma, small cell lung cancer, and hematological malignancies. This review highlights the current progress with the development of MYXV as an immunotherapeutic agent.