Impact of CD4+ T cell help on CD8+ CAR T cell gene expression during ex-vivo manufacturing

ABSTRACT: Cell culture conditions impact the clinical efficacy of chimeric antigen receptor (CAR) T cell products, but the optimal approach remains unknown. Separate CD4+ and CD8+ cultures offer a potential advantage but complicate manufacturing and may affect cell expansion and function. We evaluated the co-culture of CD4+ and CD8+ cells at a defined ratio at culture initiation. We observed that the presence of CD4+ cells markedly improves expansion of CD8+ CAR T cells, and CD8+ cells cultured in isolation exhibit a hypofunctional phenotype and transcriptional signature compared with those co-cultured with CD4+ cells. Mixed-culture CAR T cells also confer superior anti-tumor activity in vivo compared with separately expanded, co-infused cells. CD4+ cell effects on CD8+ cells are mediated through both cytokines and direct cell contact, including CD40L-CD40 and CD70-CD27 interactions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245427 | GEO | 2023/11/30

REPOSITORIES: GEO