Clinical Applications of Immunotherapy for Recurrent Glioblastoma in Adults

SIMPLE SUMMARY: There are few established treatment options for recurrent glioblastoma (rGBM). Immunotherapy, which potentiates the immune system to counter tumor growth, offers new hope for treating GBM that has relapsed after conventional therapies. The aim of this literature review is to summarize recent clinical studies of immunotherapy for rGBM, including that of immune checkpoint blockade, oncolytic virotherapy, chimeric antigen receptor (CAR) T-cell therapy, cancer vaccine and antibody-conjugated toxin. The literature search was concluded in February 2023. This review of immunotherapies provides a comprehensive overview of treatment advances, limitations in each strategy, ongoing opportunities, and preliminary correlates to survival, in order to support clinical decision-making and guide future research endeavors. ABSTRACT: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite standard therapies, including resection and chemoradiation, recurrence is virtually inevitable. Current treatment for recurrent glioblastoma (rGBM) is rapidly evolving, and emerging therapies aimed at targeting primary GBM are often first tested in rGBM to demonstrate safety and feasibility, which, in recent years, has primarily been in the form of immunotherapy. The purpose of this review is to highlight progress in clinical trials of immunotherapy for rGBM, including immune checkpoint blockade, oncolytic virotherapy, chimeric antigen receptor (CAR) T-cell therapy, cancer vaccine and immunotoxins. Three independent reviewers covered literature, published between the years 2000 and 2022, in various online databases. In general, the efficacy of immunotherapy in rGBM remains uncertain, and is limited to subsets/small cohorts of patients, despite demonstrating feasibility in early-stage clinical trials. However, considerable progress has been made in understanding the mechanisms that may preclude rGBM patients from responding to immunotherapy, as well as in developing new approaches/combination strategies that may inspire optimism for the utility of immunotherapy in this devastating disease. Continued trials are necessary to further assess the best therapeutic avenues and ascertain which treatments might benefit each patient individually.