Abstract

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13Rα2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells’ promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.

Conclusion and outlooks

CAR T cells could be a promising therapeutic option for brain cancer since so many potential target tumor antigens have been identified so far. However, one of the biggest hurdles in this field is choosing a suitable antigen to target, especially one that is expressed in brain cancer and brain cancer-initiating cells and destroys them without harming normal brain cells. Understanding the optimal trafficking of CAR T cells to brain tumors is still to be clearly interpreted. Though most clinical trials have demonstrated that CAR T cells as a monotherapy are often ineffective in cases of solid tumors due to their immune escape mechanisms, the efficacy and scope of CAR T cell therapies are continually being expanded, and innovative approaches are being explored to improve safety as well as efficacy. These innovative approaches would lead to the wider applications of this technology for the efficient management of brain cancer through the optimization of CAR T cell biology and others. However, concerns with CAR T cells also spin around their cost and scale-up, which also require substantial attention.

Abbreviations

CAR T cells:

Chimeric antigen receptor T cellsCNS:

Central nervous systemCARs:

Chimeric antigen receptorsMHC:

Major histocompatibility complexBBB:

Blood-brain barrierBBTB:

Blood-brain tumor barrierTCR:

T cell receptor TRAC:

T cell receptor α constantFDA:

Food and drug administration

Source: molecular-cancer