Safety and Efficacy of CD19-Targeted Chimeric Antigen Receptor (CAR) T-cells Generated Using DNA Transposon Systems:...

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a potentially curative approach for hematological malignancies. The DNA transposon system represents a non-viral approach to CAR T-cell generation, offering several advantages including low immunogenicity, scalability, and cost-effectiveness over existing methods. Despite significant clinical advances, no meta-analysis has been conducted to evaluate the safety and efficacy of DNA transposon-generated CAR T-cells. This meta-analysis aims to evaluate the efficacy and safety of DNA transposon-generated CAR T-cell therapy across B-cell malignancies. A systematic literature search was conducted through databases, PubMed, Google Scholar, OpenAlex, and Semantic Scholar, from 2012 to January 2024. A total of seven studies encompassing 110 patients were found eligible. The pooled analysis demonstrated an overall response rate of 75%, with a complete response achieved in 66% of patients. Moreover, 49% of patients demonstrated progression-free survival (PFS) with a median follow-up of 30 months, and 53% of patients achieved negative measurable residual disease (NMRD) remission. Notably, few patients experienced cytokine release syndrome (CRS) of grades 1-2; however, neurotoxicity was not described as a prevalent side effect. DNA transposon-generated CD19 CAR T-cell therapy demonstrates promising efficacy in B-cell malignancies, with favorable safety profiles. However, the outcomes of this meta-analysis underscore the need for further clinical development.