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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85131270967&partnerID=8YFLogxK
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 -