Scientists Hopeful About Early Study Combining Oncolytic Virus, CAR T

The combination of 2 immunotherapies—chimeric antigen receptor (CAR) T-cell therapy and an oncolytic virus—were more potent against solid tumors than CAR T-cell therapy alone in mouse models of cancer, according to a study released this week.

The study was published in Science Translational Medicine.

Anti-CD19 CAR T-cell treatment acts on the B cell antigen CD19, but not all tumors have a naturally occurring antigen that is uniformly present on tumor cells but not normal tissues.

Researchers at the City of Hope genetically engineered an oncolytic virus (OV19t) to enter tumor cells and force their expression of CD19 protein on their cell surface. The killed tumor cells released additional copies of the virus, propagating CD19 expression to adjacent tumor cells. Then, CD19-directed CAR T cells could recognize and attack these solid tumors.

The study used triple-negative breast cancer lines, as well as pancreatic, prostate, ovarian, and head and neck cancer, and also brain tumor cells. The CD19-CAR T cells were combined with OV19t in vitro and in therapeutic studies in mice.

The scientists hope that human trials testing the sequence of the oncolytic virus and CAR T could start in 2022.

In a statement, Saul Priceman, PhD, the study's senior author and an assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, said the technology had certain advantages. Solid tumors, he said, “are surrounded by a brick wall—a so-called immunosuppressive tumor microenvironment. When a CAR T cell attempts to enter the tumor, survive, and kill cancer cells, it can't effectively because of this barrier.”

Researchers said that mice already cured of their cancer with the oncolytic virus and CAR T-cell combination demonstrated prolonged protective antitumor immunity.

“The immune system built a memory response to the tumor,” said Anthony Park, PhD, a postdoctoral fellow. “Once it eradicated tumors, following the initial combination treatment, the mice were shielded against tumor recurrences.”

Park said that solid tumors are often “immunologically cold,” which means they are not typically responsive to immunotherapies; introducing the virus reversed the tumor’s harsh microenvironment, making it more receptive to CAR T-cell therapy, he said.

Reference

Park AK, Fong Y, Kim SI, et al. Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors. Sci Transl Med. 2020;(12)559:eaaz1863. doi:10.1126/scitranslmed.aaz186