CELL INTELLIGENCE · 肿瘤细胞治疗研究

Glioblastoma is a malignant brain tumor with poor outcomes. Chimeric antigen receptor-T (CAR-T)-cell therapy is a possible new intervention in solid tumors using T cells engineered with cancer-specific antigens. This approach is challenged by limited T-cell trafficking to solid tumors, the immunosuppressive tumor microenvironment, and glioblastoma-specific uncertainties. Several first-in-human trials have now trialed CAR-T therapy for glioblastoma. We undertake a systematic review of these Phase I trials to draw early lessons about the safety and feasibility of this approach.

Systematic review of all published clinical trials using CAR-T therapy for glioblastoma on July 31, 2024, from 5 databases.

Thirteen published studies of Phase I trials of CAR-T therapy for glioblastoma ( n = 128 patients). Six molecular targets were used, most commonly EGFR family (7 studies) and IL13a2 (4 studies). There were 141 severe adverse effects (SAEs) and 2 dose-limiting toxicities. SAEs were most commonly neurological or hematological, and most commonly observed with doses over 1 10 7 cells. Routes of delivery included intravenous, intraventricular, intracavitary, and intratumoral. Several participants across trials demonstrated transient responses, but efficacy across trials was difficult to compare, given heterogeneous reporting of outcomes.

Several CAR-T strategies have now been trialed preliminarily for glioblastoma. There appears to be a signal of efficacy, with 56 of 128 reported patients demonstrating at least some measure of response. Central delivery of CAR-T cells appears safe with doses up to 2.5 10 7 cells well-tolerated. Subsequent CAR-T trials should standardize reporting of outcomes for better comparison across trials.