Phase I clinical trial of EGFR-specific CAR-T cells generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer patients

Key findings

Zhang et al. conducted a phase I clinical trial evaluating EGFR-targeted CAR-T cells manufactured using the piggyBac transposon system in patients with advanced relapsed or refractory non-small cell lung cancer (NSCLC). The non-viral piggyBac-based approach achieved efficient CAR transgene integration into patient T cells, generating clinically relevant cell products with stable CAR expression.

Ten enrolled patients received autologous EGFR-CAR-T cells at doses ranging from 0.4×10⁶ to 2.1×10⁶ cells/kg. The piggyBac system demonstrated acceptable safety profiles with no dose-limiting toxicities or cytokine release syndrome above grade 2. CAR-T cells expanded in vivo and persisted in peripheral blood for up to 12 months post-infusion in responding patients.

Clinical efficacy showed 1 partial response (10%), 6 stable disease cases (60%), and 3 progressive disease cases (30%), with a disease control rate of 70%. Median progression-free survival reached 4.0 months. The trial validated piggyBac transposon-mediated CAR-T cell manufacturing as a viable non-viral alternative to lentiviral vectors for clinical gene therapy applications, offering advantages in production scalability and reduced immunogenicity concerns.