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
CAR T-cell manufacturing relied on costly viral vectors with genotoxicity risk. A phase I trial tested piggyBac-generated EGFR-CAR T cells in nine NSCLC patients. Infusions caused no grade 4 events, and one patient had a 13-month partial response.
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.
Abstract
Purpose: This phase I clinical trial assessed the safety and feasibility of epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR) T cells generated by the piggyBac transposon system in advanced relapsed/refractory EGFR-positive non-small cell lung cancer (NSCLC). Methods: Nine patients received two treatment cycles at 1 × 10^6 or 3 × 10^6 cells/kg. Results: Infusions were well tolerated, most adverse events were grade 1-3 fever, and no grade 4 toxicity or severe cytokine release syndrome was observed.