Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients

Abstract

Improving the chances of curing cancer patients who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, non-randomized biological endpoint study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the pre-surgical intravenous (i.v.) delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases (CRLM) or metastatic melanoma were treated with a single i.v. infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side-effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells (PBMCs). Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with interferon-α secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anti-cancer immunity. In the two patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of pre-surgical oncolytic vaccinia virus-based therapies to stimulate anti-cancer immunity and increase the chances to cure patients with cancer.