TY - JOUR
T1 - Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma
AU - Makielski, Kelly M.
AU - Sarver, Aaron L.
AU - Henson, Michael S.
AU - Stuebner, Kathleen M.
AU - Borgatti, Antonella
AU - Suksanpaisan, Lukkana
AU - Preusser, Caitlin
AU - Tabaran, Alexandru Flaviu
AU - Cornax, Ingrid
AU - O'Sullivan, M. Gerard
AU - Chehadeh, Andrea
AU - Groschen, Donna
AU - Bergsrud, Kelly
AU - Pracht, Sara
AU - Winter, Amber
AU - Mills, Lauren J.
AU - Schwabenlander, Marc D.
AU - Wolfe, Melissa
AU - Farrar, Michael A.
AU - Cutter, Gary R.
AU - Koopmeiners, Joseph S.
AU - Russell, Stephen J.
AU - Modiano, Jaime F.
AU - Naik, Shruthi
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/12/19
Y1 - 2023/12/19
N2 - Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNβ-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNβ-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a “tail” of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.
AB - Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNβ-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNβ-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a “tail” of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.
KW - antitumor immunity
KW - immunotherapy
KW - neoadjuvant
KW - oncolytic virus
KW - osteosarcoma
KW - tumor microenvironment
KW - vesicular stomatitis virus
KW - virotherapy
UR - http://www.scopus.com/inward/record.url?scp=85175254616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85175254616&partnerID=8YFLogxK
U2 - 10.1016/j.omto.2023.100736
DO - 10.1016/j.omto.2023.100736
M3 - Article
AN - SCOPUS:85175254616
SN - 2372-7705
VL - 31
JO - Molecular Therapy Oncolytics
JF - Molecular Therapy Oncolytics
M1 - 100736
ER -