Figure 1.

Designing safe, effective, and long-lasting T-cell therapies for PBTs. (A) Scheme representing CAR T–cell treatment via adoptive T cell transfer in pediatric patients with brain tumors. (1) T cells are isolated from patient’s blood followed by (2) T cell activation and reprograming in the lab to express the chimeric antigen receptor (CAR) using viral vectors. (3) CAR T–cells are then expanded, and they undergo quality control testing (4) prior to infusion into the patient (5). (B) Key questions to address when designing CAR T–cells for PBTs. (1) Selecting an appropriate target: Several TAAs (including IL13Rα2, EphA2, B7-H3, GD2, EGFRvIII, and TNC) are expressed in PBTs with heterogenous expression patterns. (2) Overcoming the suppressive immune TME: Immune cells (like TAMs, DCs, Tregs, and EOs) infiltrate PBTs and they induce different immune interactions that affect the CAR T–cells’ ability to perform their cytotoxic properties. (3) Once infused, CAR T–cells need to home to the patient’s tumor and exert their cytolytic activity while expanding and persisting to create long-lasting effects.