CD8⁺ chimeric antigen receptor T cells manufactured in absence of CD4⁺ cells exhibit hypofunctional phenotype.

ABSTRACT:

Background

Cell culture conditions during manufacturing can impact the clinical efficacy of chimeric antigen receptor (CAR) T cell products. Production methods have not been standardized because the optimal approach remains unknown. Separate CD4⁺ and CD8⁺ cultures offer a potential advantage but complicate manufacturing and may affect cell expansion and function. In a phase 1/2 clinical trial, we observed poor expansion of separate CD8⁺ cell cultures and hypothesized that coculture of CD4⁺ cells and CD8⁺ cells at a defined ratio at culture initiation would enhance CD8⁺ cell expansion and simplify manufacturing.

Methods

We generated CAR T cells either as separate CD4⁺ and CD8⁺ cells, or as

SUBMITTER: Lee SY 

PROVIDER: S-EPMC10660840 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature