Umbilical cord blood: A promising source for allogeneic CAR-T cells

Dian-Dian Liu; Wei-Cong Hong; Kun-Yin Qiu; Xin-Yu Li; Yong Liu; Li-Wen Zhu; Wei-Xin Lai; Han- Chen; Hua-Qing Yang; Lu-Hong Xu; Jian-Pei Fang

doi:10.3389/fonc.2022.944248

Umbilical cord blood: A promising source for allogeneic CAR-T cells

Front Oncol. 2022 Jul 29:12:944248. doi: 10.3389/fonc.2022.944248. eCollection 2022.

Authors

Dian-Dian Liu^{1

2}, Wei-Cong Hong^{1

2}, Kun-Yin Qiu^{1

2}, Xin-Yu Li^{1

2}, Yong Liu^{1

2}, Li-Wen Zhu^{1

2}, Wei-Xin Lai^{1

2}, Han- Chen^{1

2}, Hua-Qing Yang^{1

2}, Lu-Hong Xu^{1

2}, Jian-Pei Fang^{1

2}

Affiliations

¹ Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
² Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, China.

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.

Keywords: NCG-immunodeficient mice; T-lymphocyte subsets; acute lymphoblastic leukemia; chimeric antigen receptor T cells; peripheral blood; umbilical cord blood.