AUTHOR=Liu Dian-Dian , Hong Wei-Cong , Qiu Kun-Yin , Li Xin-Yu , Liu Yong , Zhu Li-Wen , Lai Wei-Xin , Chen Han- , Yang Hua-Qing , Xu Lu-Hong , Fang Jian-Pei TITLE=Umbilical cord blood: A promising source for allogeneic CAR-T cells JOURNAL=Frontiers in Oncology VOLUME=Volume 12 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.944248 DOI=10.3389/fonc.2022.944248 ISSN=2234-943X ABSTRACT=

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed and refractory acute lymphoblastic leukemia (R/R ALL). However, autologous CAR-T cells derived from patients with B-ALL often show poor amplification ability, exhaustion, and anergy. To overcome these limitations, allogeneic CAR-T cells may be used as effective substitutes; however, which source would be the best substitute is unclear. In this study, we compared the immunophenotype and antitumor efficacy of anti-CD19 CAR-T cells derived from healthy donor cord blood (CB), healthy donor peripheral blood (PB), and PB of B-ALL patients [PB (patient)] in vitro and NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG)-immunodeficient mice, respectively. The results revealed that CAR-T cells derived from healthy donor CB and PB showed a higher proportion of naive T cells and longer tumor suppression in tumor-bearing mice than those of PB (patient). PB (patient) CAR-T cells had a higher proportion of regulatory T cells (Treg cells) and released high levels of interluekin-10 (IL-10), which also suggest a poor prognosis. Thus, CAR-T cells derived from healthy donors have better antitumor efficacy than CAR-T cells derived from PB (patient), and CB may be a good source of allogeneic CAR-T cells.