A meta-analysis on safety and efficacy of CD19 directed CAR T-cells generated using sleeping beauty transposon system

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a potentially curative approach for hematological malignancies. The sleeping beauty (SB) 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, the efficacy and safety of SB-generated CAR T-cells have not been adequately addressed. This meta-analysis aims to evaluate the efficacy and safety of SB-generated CAR T-cell therapy across B-cell malignancies. A systematic literature search was conducted through databases, PubMed, Google Scholar, Open Alex, and Semantic scholar from 2012 to January 2024. A total of 10 studies encompassing 153 patients were found eligible. The pooled analysis demonstrated an overall response rate of 71%, with complete response achieved in 66% of patients. Moreover, 55% of patients demonstrated progression-free survival (PFS) with a median follow-up of 30 months and 55% of patients achieved measurable residual disease (MRD) negative remission. Notably, few patients experienced cytokine release syndrome (CRS) of grade 1-2; however, neurotoxicity were not described as prevalent side effects. SB-generated anti-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. PROSPERO registration No. CRD42024507597. Keywords: CD19, hematological malignancies, sleeping beauty chimeric antigen receptor, meta-analysis, clinical trial, non-viral gene transfer. PROSPERO registration No. CRD42024507597.