Anti-GITR therapy promotes immunity against malignant glioma in a murine model

In this study, we examined the modality of the antibody function at the tumor site as opposed to the periphery as the blood –brain barrier prevents efficient antibody delivery to brain tumors. Mice harboring established GL261 tumors were treated with anti-GITR monotherapy and were shown to have a significant increase in overall survival (p <  0.01) when antibodies were injected directly into the glioma core, whereas peripheral antibody treatment only had a modest effect. Peripheral treatment resulted in a significant decrease in granzyme B (GrB) expression by Tregs, whereas intratumoral treatment resulted in both a decrease in GrB expr ession by Tregs and their selective depletion, which was largely mediated by FcγR-mediated destruction. We also discovered that anti-GITR treatment results in the enhanced survival and functionality of dendritic cells (DCs)—a previously unreported effect of this immunotherapy. In effect, this stu dy demonstrates that the targeting of GITR is a feasible and noteworthy treatment option for glioma, but is largely dependent on the anatomical location in which the antibodies are delivered.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research