Endogenous retrovirus envelope as a tumor-associated immunotherapeutic target in murine osteosarcoma
Mary Frances Wedekind,
Katherine E. Miller,
Chun-Yu Chen,
Pin-Yi Wang,
Brian J. Hutzen,
Mark A. Currier,
Brooke Nartker,
Ryan D. Roberts,
Louis Boon,
Joe Conner,
Stephanie LaHaye,
Benjamin J. Kelly,
David Gordon,
Peter White,
Elaine R. Mardis,
Timothy P. Cripe
Affiliations
Mary Frances Wedekind
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA; Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, The Ohio State University, Columbus, OH, USA
Katherine E. Miller
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
Chun-Yu Chen
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA
Pin-Yi Wang
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA
Brian J. Hutzen
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA
Mark A. Currier
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA
Brooke Nartker
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA
Ryan D. Roberts
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA; Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, The Ohio State University, Columbus, OH, USA
Louis Boon
Polpharma Biologics, Utrecht, the Netherlands
Joe Conner
Virttu Biologics, Ltd, Glasgow, UK
Stephanie LaHaye
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
Benjamin J. Kelly
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
David Gordon
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
Peter White
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
Elaine R. Mardis
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
Timothy P. Cripe
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA; Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, The Ohio State University, Columbus, OH, USA; Corresponding author
Summary: Osteosarcoma remains one of the deadliest cancers in pediatrics and young adults. We administered two types of immunotherapies, oncolytic virotherapy and immune checkpoint inhibition, to two murine osteosarcoma models and observed divergent results. Mice bearing F420 showed no response, whereas those with K7M2 showed prolonged survival in response to combination therapy. K7M2 had higher expression of immune-related genes and higher baseline immune cell infiltrates, but there were no significant differences in tumor mutational burden or predicted MHC class I binding of nonsynonymous mutations. Instead, we found several mouse endogenous retrovirus sequences highly expressed in K7M2 compared with F420. T cell tetramer staining for one of them, gp70, was detected in mice with K7M2 but not F420, suggesting that endogenous retrovirus proteins are targets for the anti-tumor immune reaction. Given prior observations of endogenous retrovirus expression in human osteosarcomas, our findings may be translatable to human disease.
