Choice of activation protocol impacts the yield and quality of CAR T cell product, particularly with older individuals
- Author(s)
- Mehta, PH; Trollope, GS; Leung, P; Chinni, SS; Iasinskaia, A; Harrison, AJ; Hughes-Parry, H; Jenkins, MR; Kershaw, MH; Jaworowski, A; Slaney, CY; Koldej, RM; Ritchie, DS; Quinn, KM;
- Details
- Publication Year 2024,Volume 13,Issue #12,Page e70016
- Journal Title
- Clinical & Translational Immunology
- Publication Type
- Research article
- Abstract
- OBJECTIVES: In clinical chimeric antigen receptor (CAR) T cell therapy, one of the strongest correlates of favorable patient responses is lower levels of differentiation in T cells from the peripheral blood mononuclear cell (PBMC) starting material or the CAR T cell product. T cells from older patients are inherently more differentiated, but we hypothesised that specific activation protocols could be used to limit CAR T cell differentiation during manufacturing, particularly in older patients. METHODS: We used PBMCs from young (20-30 years old) and older (60+ years old) healthy donors to generate CAR T cells using two activation protocols: soluble anti-(α) CD3 monoclonal antibody (mAb) vs immune complexes of αCD3 and αCD28 mAbs. Products were assessed for yield, function and differentiation, which was used as a measure of CAR T cell quality. T cells in PBMCs were assessed for CD28 expression and correlative analyses were performed. RESULTS: Older samples generated fewer, more differentiated CAR T cells than young samples, and the αCD3/CD28 mAb protocol exacerbated this, further reducing yield and quality. CD28 expression by T cells correlated with CAR T cell differentiation, but T cell differentiation in PBMC starting material was a stronger correlate of CAR T cell differentiation. CONCLUSIONS: Choice of activation protocol can substantially impact on the yield and quality of CAR T cells during manufacturing. This is a key consideration for older patients whose samples already generate a poorer yield and lower quality of CAR T cells.
- Publisher
- Wiley
- Keywords
- CAR T cell; Cd28; T cell activation; ageing
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1002/cti2.70016
- Open Access at Publisher's Site
https://doi.org/10.1002/cti2.70016- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-17 06:20:07
Last Modified: 2024-12-17 06:26:01