TY - JOUR
T1 - Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients
AU - Samson, Adel
AU - West, Emma J.
AU - Carmichael, Jonathan
AU - Scott, Karen J.
AU - Turnbull, Samantha
AU - Kuszlewicz, Bethany
AU - Dave, Rajiv V.
AU - Peckham-Cooper, Adam
AU - Tidswell, Emma
AU - Kingston, Jennifer
AU - Johnpulle, Michelle
AU - da Silva, Barbara
AU - Jennings, Victoria A.
AU - Bendjama, Kaidre
AU - Stojkowitz, Nicolas
AU - Lusky, Monika
AU - Prasad, K. R.
AU - Toogood, Giles J.
AU - Auer, Rebecca
AU - Bell, John
AU - Twelves, Chris J.
AU - Harrington, Kevin J.
AU - Vile, Richard G.
AU - Pandha, Hardev
AU - Errington-Mais, Fiona
AU - Ralph, Christy
AU - Newton, Darren J.
AU - Anthoney, Alan
AU - Melcher, Alan A.
AU - Collinson, Fiona
N1 - Funding Information:
We are grateful to all the patients that participated in this trial. The research was supported by the National Institute for Health Research (NIHR) infrastructure and the Experimental Cancer Medicine Centre (ECMC) at Leeds. A. Samson was supported by fellowships from Yorkshire Cancer Research (YCR) and Cancer Research UK (CRUK). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Funding Information:
We are grateful to all the patients that participated in this trial. The research was supported by the National Institute for Health Research (NIHR) infrastructure and the Experimental Cancer Medicine Centre (ECMC) at Leeds. A. Samson was supported by fellowships from Yorkshire Cancer Research (YCR) and Cancer Research UK (CRUK). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Transgene, Strasbourg, Yorkshire Cancer Research, Cancer Research UK and the Institute of Cancer Research/Royal Marsden NIHR Biomedical Research Centre.
Funding Information:
A. Samson reports grants from Transgene during the conduct of the study. K.J. Scott reports grants from Transgene during the conduct of the study. K. Bendjama reports personal fees from Transgene SA during the conduct of the study. N. Stojkowitz reports personal fees from Transgene outside the submitted work. J. Bell reports other support from Jennerex Biotherapeutics during the conduct of the study; other support from Jennerex Biotherapeutics outside the submitted work; in addition, J. Bell has a patent for WO2013022764A1d pending. K.J. Harrington reports personal fees from Arch Oncology, BMS, Inzen, Merck-Serono, Pfizer; grants and personal fees from AstraZeneca, Boehringer-Ingelheim, MSD, and Replimune outside the submitted work. C. Ralph reports grants from Jennerex during the conduct of the study; grants from Oncolytics Biotech, nonfinancial support from Viralytics, personal fees and non-financial support from BMS and Eisai outside the submitted work. A. Anthoney reports grants and personal fees from Transgene during the conduct of the study. F. Collinson reports grants from Transgene during the conduct of the study. No disclosures were reported by the other authors.
Publisher Copyright:
© 2022 The Authors; Published by the American Association for Cancer Research
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85131270967&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-21-0171
DO - 10.1158/2326-6066.CIR-21-0171
M3 - Article
C2 - 35439304
AN - SCOPUS:85131270967
SN - 2326-6066
VL - 10
SP - 745
EP - 756
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 6
ER -