Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anti-Cancer Immunity in Patients
Menée à l'aide d'échantillons sanguins et d'échantillons tissulaires prélevés sur 9 patients atteints d'un mélanome métastatique ou présentant des métastases hépatiques ayant pour origine un cancer colorectal, cette étude met en évidence l'intérêt d'une injection intraveineuse du virus de la vaccine avant la résection des métastases pour améliorer l'immunité antitumorale
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.