Comparison Of Two Process Protocols For Allogeneic CAR-T Production With Reduced Cost

This study explores the development of allogenic chimeric antigen receptor T cells (CAR-T cells) for the treatment of B-cell malignancies. While autologous CAR-T cell therapy demonstrates remarkable efficacy, limitations associated with manufacturing time, cost, and scalability necessitate the investigation of alternative approaches. Here, we present a novel allogenic CAR-T cell production process utilizing CRISPR-Cas9 technology for the targeted ablation of TRAC and CD52 genes in donor T cells. This strategy aims to mitigate the risk of graft-versus-host disease (GVHD) and establish compatibility with anti-CD52-based lymphodepleting regimens.

Our findings establish a robust allogenic CAR-T cell production process utilizing either cryopreserved T cells from a bank or peripheral blood mononuclear cells (PBMCs). Employing the T cell bank, a high T cell selection recovery rate exceeding 60% was achieved. Furthermore, an economical alternative process utilizing PBMCs as the starting material was developed. While this approach might be impacted by the efficiency of T cell selection from PBMCs, both production methods demonstrably meet established release criteria. Explore how this paves the way for further investigation of allogenic CAR-T cell therapy as a potentially more accessible and cost-effective treatment option.