Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients

Adel Samson, Emma J. West, Jonathan Carmichael, Karen J. Scott, Samantha Turnbull, Bethany Kuszlewicz, Rajiv V. Dave, Adam Peckham-Cooper, Emma Tidswell, Jennifer Kingston, Michelle Johnpulle, Barbara da Silva, Victoria A. Jennings, Kaidre Bendjama, Nicolas Stojkowitz, Monika Lusky, K. R. Prasad, Giles J. Toogood, Rebecca Auer, John BellChris J. Twelves, Kevin J. Harrington, Richard G. Vile, Hardev Pandha, Fiona Errington-Mais, Christy Ralph, Darren J. Newton, Alan Anthoney, Alan A. Melcher, Fiona Collinson

Research output: Contribution to journalArticlepeer-review

Abstract

Improving the chances of curing patients with cancer 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, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous 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. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNa secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 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 presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.

Original languageEnglish (US)
Pages (from-to)745-756
Number of pages12
JournalCancer Immunology Research
Volume10
Issue number6
DOIs
StatePublished - Jun 2022

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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