Unravelling the modified T cell receptor through Gen-Next CAR T cell therapy in Glioblastoma: Current status and future challenges

Abstract

Purpose

Despite current technological advancements in the treatment of glioma, immediate alleviation of symptoms can be catered by therapeutic modalities, including surgery, chemotherapy, and combinatorial radiotherapy that exploit aberrations of glioma. Additionally, a small number of target antigens, their heterogeneity, and immune evasion are the potential reasons for developing targeted therapies. This oncologic milestone has catalyzed interest in developing immunotherapies against Glioblastoma to improve overall survival and cure patients with high-grade glioma. The next-gen CAR-T Cell therapy is one of the effective immunotherapeutic strategies in which autologous T cells have been modified to express receptors against GBM and it modulates cytotoxicity.

Methods

In this review article, we examine preclinical and clinical outcomes, and limitations as well as present cutting-edge techniques to improve the function of CAR-T cell therapy and explore the possibility of combination therapy.

Findings

To date, several CAR T-cell therapies are being evaluated in clinical trials for GBM and other brain malignancies and multiple preclinical studies have demonstrated encouraging outcomes.

Implications

CAR-T cell therapy represents a promising therapeutic paradigm in the treatment of solid tumors but a few limitations include, the blood-brain barrier (BBB), antigen escape, tumor microenvironment (TME), tumor heterogeneity, and its plasticity that suppresses immune responses weakens the ability of this therapy. Additional investigation is required that can accurately identify the targets and reflect the similar architecture of glioblastoma, thus optimizing the efficiency of CAR-T cell therapy; allowing for the selection of patients most likely to benefit from immuno-based treatments.