Generation of Oncolytic Virus Induced Tumour-Infiltrating Lymphocytes (TILs) for the Treatment of Solid Tumours

Abstract

Colorectal cancer is the third most common and second deadliest cancer globally, necessitating new therapies. Combining two immunotherapies, tumour-infiltrating lymphocytes (TILs) and oncolytic viruses, shows promise in improving patient outcomes. While showing promise in select solid cancers, TIL therapy has been limited due to the scarcity of tumour-specific lymphocytes within the tumour. Preliminary studies have shown that oncolytic virus pre-administration increases the number of antitumour lymphocytes within the tumour that can be harvested for adoptive cell therapy. Using an MC38 colorectal tumour model in C57BL/6 mice, we determined the impact of oncolytic viruses on TILs that can be harvested for adoptive cell therapy. The relationship between oncolytic virus pre-administration and TIL composition was characterized using flow cytometry, immune assays, and adoptive cell therapy studies. Oncolytic virus-induced TILs showed greater tumour-specificity and promoted greater antitumour control. Our approach would increase the capacity for TIL therapy to be used in the treatment of more types of solid tumours, including colorectal cancer.