Anti-CD19 chimeric antigen receptor (CAR) T cells made from umbilical cord blood cells (UCB) had a distinct phenotype from anti-CD19 CAR T cells made from peripheral blood-derived T lymphocytes (PBL), according to a study recently reported at the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer, or SITC 2019.1
Although CAR-T therapies generated from T lymphocytes have demonstrated their safety and efficacy and are commercially available, they must be made on a patient-by-patient basis. The study authors reasoned that UCB cells represent an “appealing” starting material to make off-the shelf CAR-T cells because the cells have a “unique capacity” for broad leukocyte antigen-matching.
CAR T cells were produced from UCB from 5 healthy donors and from PBL from 2 healthy donors. Both sets of cells were successfully transduced. The UCB-derived CAR T cells had higher proportions of CD4+ T cells compared with PBL-derived CAR T cells (45%-59% vs 27%-36%). The UCB-derived CAR T cells had lower proportions of CD8+ T cells compared with PBL-derived CAR T cells (18%-20% vs 40%-67%).
Several differing characteristics were also observed. UCB-derived CAR T cells were enriched for a specific phenotype (ie, CD45RA+CCR7+CD27+CD62L+ T cells), and only UCB-derived CAR T cells expressed the costimulatory proteins ICOS and 4-1BB. In contrast, only PBL-derived CAR T cells had markers indicative of late differentiation/exhaustion of T cells.
Other differences included UCB-derived CAR T cells having higher expression levels of PD-L1 and the gene-expression profiles differing between UCB- and PBL-derived CAR T cells.
Both UCB- and PBL-derived CAR T cells, however, showed antigen-specific reactivity against acute lymphoblastic leukemia or Epstein-Barr virus B cells overexpressing CD19.
“Taken together, these results proved that antitumor early differentiated/central memory CAR-T cells can be efficiently isolated from UCB with distinctive phenotype as compared to PBL-CAR-T cells,” the study authors wrote in conclusion.
Maccalli C, Kizhakayil D, Ravindran S, et al. Comparison of phenotype and anti-tumor profile of CD19-CAR-T cells generated from either umbilical cord blood- or peripheral blood-derived T lymphocytes. Poster presented at: the 34th Annual Meeting & Preconference Programs (SITC 2019); November 6–10, 2019: National Harbor, Maryland. Abstract P201.