Research Alert
Abstract (ID): 383
Newswise — Malignant gliomas are deadly brain tumors with no cure. We engineered herpes simplex virus (HSV)-1 and developed oncolytic HSV (oHSV) to treat brain tumors, given its potential to selectively kill tumor cells while sparing normal brain cells, and to boost anti-tumor immunity. The therapy shows great promise based on our Phase I trial results. However, the precise mechanisms for its enhanced anti-tumor immune responses remain poorly understood. Using an oHSV secreting murine IL-12 (M002), murine intracranial glioma models and adoptive transfer approaches, we observed that M002 treatment induced unique CD4+ T-cell populations to acquire cytolytic effector phenotypes, promoting anti-glioma responses in an MHCII-dependent manner. Notably, single-cell RNA sequencing and T-cell receptor (TCR) repertoire analysis revealed that M002 treatment shifted the TCR dominance while reducing the clonal diversity. These results suggest that the capacity of oncolytic virus therapy to reshape the anti-tumor CD4+ T-cell repertoire contributes to its improved efficacy. Insights obtained from this study can facilitate the development of better therapeutic strategies for brain tumor patients.
Supported by DoD W81XH-18-1-0315 and UAB Faculty Start-up Funds. J.M.M. received payments from structured buyout of Catherex, Inc. which was purchased by Amgen in 2015 and no longer exists. J.M.M. also has equity in and has received royalties from Aettis, Inc., which holds frozen oncolytic viral stocks.
J.M.M. is a co-owner of Treovir, Inc which holds a small business innovation research fund to execute a clinical trial of G207 in pediatric patients. J.M.M. has served as a consultant for Imugene. J.M.M. holds intellectual property for another oncolytic virus, C134, which has been licensed to Mustang Bio, Inc., but is blinded to the specifics of the relationship.
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