Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients.
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Embargo End Date
ICR Authors
Authors
Samson, A
West, EJ
Carmichael, J
Scott, KJ
Turnbull, S
Kuszlewicz, B
Dave, RV
Peckham-Cooper, A
Tidswell, E
Kingston, J
Johnpulle, M
da Silva, B
Jennings, VA
Bendjama, K
Stojkowitz, N
Lusky, M
Prasad, KR
Toogood, GJ
Auer, R
Bell, J
Twelves, CJ
Harrington, KJ
Vile, RG
Pandha, H
Errington-Mais, F
Ralph, C
Newton, DJ
Anthoney, A
Melcher, AA
Collinson, F
West, EJ
Carmichael, J
Scott, KJ
Turnbull, S
Kuszlewicz, B
Dave, RV
Peckham-Cooper, A
Tidswell, E
Kingston, J
Johnpulle, M
da Silva, B
Jennings, VA
Bendjama, K
Stojkowitz, N
Lusky, M
Prasad, KR
Toogood, GJ
Auer, R
Bell, J
Twelves, CJ
Harrington, KJ
Vile, RG
Pandha, H
Errington-Mais, F
Ralph, C
Newton, DJ
Anthoney, A
Melcher, AA
Collinson, F
Document Type
Journal Article
Date
2022-06-03
Date Accepted
2022-04-15
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 IFNα 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.
Citation
Cancer immunology research, 2022
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
2326-6066
eISSN
2326-6074
2326-6074
2326-6074
Research Team
Targeted Therapy