CAR T cell therapy for pediatric central nervous system tumors: a review of the literature and current North American trials.

in Cancer metastasis reviews by Rebecca Ronsley, Kelsey C Bertrand, Edward Z Song, Andrea Timpanaro, Michelle Choe, Dana Tlais, Nicholas A Vitanza, Julie R Park

TLDR

  • Chimeric antigen receptor T (CAR T) cell therapy is a new way to treat brain tumors in children. It works by using a special kind of cell called a T cell to fight the tumor. The T cell is genetically modified to recognize a specific protein on the surface of the tumor cells. This allows the T cell to target and destroy the tumor cells. The study looked at the evidence from preclinical experiments and clinical trials to see how well CAR T cell therapy works and if it is safe. The results showed that CAR T cell therapy is effective in treating some types of brain tumors, but it can also be dangerous. The study also looked at how well the therapy works and how it can be improved in the future.

Abstract

Central nervous system (CNS) tumors are the leading cause of cancer-related death in children. Typical therapy for CNS tumors in children involves a combination of surgery, radiation, and chemotherapy. While upfront therapy is effective for many high-grade tumors, therapy at the time of relapse remains limited. Furthermore, for diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), there are currently no curative therapies. Chimeric antigen receptor T (CAR T) cell therapy is a promising novel treatment avenue for these tumors. Here, we review the preclinical evidence for CAR T cell use in pediatric brain tumors, the preliminary clinical experience of CNS CAR T cell trials, toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors, challenges in disease response evaluation with CAR T cell therapy, and the knowledge gained from correlative biologic studies from these trials in the pediatric and young adult population.

Overview

  • The study focuses on the use of chimeric antigen receptor T (CAR T) cell therapy as a novel treatment avenue for central nervous system (CNS) tumors in children. The hypothesis being tested is the effectiveness and safety of CAR T cell therapy in pediatric brain tumors, particularly in diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG).
  • The methodology used for the experiment includes a review of preclinical evidence for CAR T cell use in pediatric brain tumors, analysis of preliminary clinical experience of CNS CAR T cell trials, examination of toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors, evaluation of challenges in disease response evaluation with CAR T cell therapy, and analysis of correlative biologic studies from these trials in the pediatric and young adult population.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The preclinical evidence suggests that CAR T cell therapy is effective in pediatric brain tumors, particularly in DIPG and DMG. The preliminary clinical experience of CNS CAR T cell trials shows promising results, with some patients achieving durable responses. However, the toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors is significant, and challenges in disease response evaluation with CAR T cell therapy need to be addressed. The knowledge gained from correlative biologic studies from these trials in the pediatric and young adult population provides insights into the mechanisms of disease and potential targets for future CAR T cell therapy development.

Implications and Future Directions

  • The study's findings suggest that CAR T cell therapy is a promising novel treatment avenue for pediatric brain tumors, particularly in DIPG and DMG. However, the toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors needs to be addressed, and challenges in disease response evaluation with CAR T cell therapy need to be addressed. Future research directions could include the development of safer and more effective CAR T cell therapies, the exploration of combination therapies with other modalities, and the evaluation of CAR T cell therapy in other pediatric brain tumors. Additionally, further correlative biologic studies are needed to better understand the mechanisms of disease and potential targets for future CAR T cell therapy development.
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