Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells.

ABSTRACT: Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and characterized a potent, fully human anti-MSLN CAR. In a phase 1 dose-escalation study of patients with solid tumors, we observed two cases of severe pulmonary toxicity following intravenous infusion of this product in the high-dose cohort (1-3 × 10⁸ T cells per m²). Both patients demonstrated progressive hypoxemia within 48 h of infusion with clinical and laboratory findings consistent with cytokine release syndrome. One patient ultimately progressed to grade 5 respiratory failure. An autopsy revealed acute lung injury, extensiv

SUBMITTER: Haas AR 

PROVIDER: S-EPMC10422001 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature