To investigate the timing of CAR T cell administration in relation to glioblastoma surgery and its effects on tumor control and survival.
Approach:
Study Design: The study utilized two mouse models and patient-derived glioblastoma tissue cultured ex vivo to assess immune changes and treatment efficacy.
Treatment Timing: GD2-targeting CAR T cells were administered either three days before surgery or during the surgical procedure to evaluate differences in outcomes.
Key Findings:
Preoperative CAR T cell treatment improved tumor control and prolonged survival compared to postoperative treatment or surgery alone.
Surgery induced changes in the tumor microenvironment, increasing TREM2 levels and leading to T cell exhaustion.
CAR T cells administered before surgery showed stronger effector function and better distribution around the tumor compared to those given during surgery, which were largely confined to the cavity and showed more signs of exhaustion.
Interpretation:
The timing of CAR T cell administration relative to surgery significantly impacts treatment efficacy in glioblastoma.
Limitations:
The study's treatment efficacy was tested only in male mice.
Mouse models do not fully replicate the complexity of the human glioblastoma immune environment.
Conclusion:
The Geneva team plans to initiate a phase I trial in newly diagnosed patients, with potential modifications to evaluate preoperative CAR T treatment.
