Photo Credit: Meletios Verras
The following is a summary of “Construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments,” published in the March 2024 issue of Oncology by Chen et al.
Chimeric antigen receptor-T (CAR-T) cell therapy has emerged as a promising immunotherapeutic strategy, yet its widespread application is hampered by logistical challenges such as lengthy preparation times, high costs, and interpatient variability. While the development of universal CAR-T (U-CAR-T) cells has addressed some of these concerns, cell banks’ lack of stability and uniformity still needs to be addressed. In this study, the researchers aimed to enhance the convenience and versatility of U-CAR-T cells by engineering modular universal CAR-T (MU-CAR-T) cells. The study group began by selecting healthy donors and isolating T cells enriched for stem cell-like memory T (TSCM) cells, known for their robust self-renewal and cytotoxicity. They employed CRISPR/Cas9 technology to double-knockout the T cell receptor (TCR) and class I human leukocyte antigen (HLA-I) genes to mitigate alloreactivity.
The resulting genetically stable universal cells were stored as a standardized cell bank. Subsequently, the investigators utilized the SDcatcher/GVoptiTag system to covalently attach purified single-chain variable fragments (scFvs) of antibodies targeting different antigens to the recovered CAR-T cells. The engineered CAR-T cells exhibited specific functionality against diverse targets, including eradicating human immunodeficiency virus type 1 (HIV-1)-latently infected cells and eliminating T lymphoma cells, with efficacy comparable to traditional CAR-T cells.
Overall, their approach facilitates the modular production of CAR-T cells, streamlining quality control and pharmaceutical manufacturing processes for broader clinical implementation.
Source: molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-01938-8