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脐带血作为低分化T细胞来源用于生产CD123嵌合抗原受体T细胞

Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells.

作者信息

Caël Blandine, Galaine Jeanne, Bardey Isabelle, Marton Chrystel, Fredon Maxime, Biichle Sabeha, Poussard Margaux, Godet Yann, Angelot-Delettre Fanny, Barisien Christophe, Bésiers Christophe, Adotevi Olivier, Pouthier Fabienne, Garnache-Ottou Francine, Bôle-Richard Elodie

机构信息

RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, EFS BFC, INSERM, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.

Activité d'Ingénierie Cellulaire et Tissulaire, Etablissement Français du Sang Bourgogne/Franche-Comté, F-25000 Besançon, France.

出版信息

Cancers (Basel). 2022 Jun 28;14(13):3168. doi: 10.3390/cancers14133168.

DOI:10.3390/cancers14133168
PMID:35804941
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9264759/
Abstract

Chimeric Antigen Receptor (CAR) therapy has led to great successes in patients with leukemia and lymphoma. Umbilical Cord Blood (UCB), stored in UCB banks, is an attractive source of T cells for CAR-T production. We used a third generation CD123 CAR-T (CD28/4-1BB), which was previously developed using an adult's Peripheral Blood (PB), to test the ability of obtaining CD123 CAR-T from fresh or cryopreserved UCB. We obtained a cell product with a high and stable transduction efficacy, and a poorly differentiated phenotype of CAR-T cells, while retaining high cytotoxic functions in vitro and in vivo. Moreover, CAR-T produced from cryopreserved UCB are as functional as CAR-T produced from fresh UCB. Overall, these data pave the way for the clinical development of UCB-derived CAR-T. UCB CAR-T could be transferred in an autologous manner (after an UCB transplant) to reduce post-transplant relapses, or in an allogeneic setting, thanks to fewer HLA restrictions which ease the requirements for a match between the donor and recipient.

摘要

嵌合抗原受体（CAR）疗法已在白血病和淋巴瘤患者中取得了巨大成功。储存在脐带血库中的脐带血（UCB）是用于生产CAR-T的T细胞的一个有吸引力的来源。我们使用了第三代CD123 CAR-T（CD28/4-1BB），其先前是使用成人外周血（PB）开发的，以测试从新鲜或冷冻保存的UCB中获得CD123 CAR-T的能力。我们获得了一种具有高且稳定转导效率以及CAR-T细胞低分化表型的细胞产品，同时在体外和体内均保留了高细胞毒性功能。此外，由冷冻保存的UCB产生的CAR-T与由新鲜UCB产生的CAR-T具有相同的功能。总体而言，这些数据为UCB来源的CAR-T的临床开发铺平了道路。UCB CAR-T可以以自体方式（在UCB移植后）进行移植以减少移植后复发，或者在同种异体环境中进行移植，这得益于较少的HLA限制，从而放宽了对供体和受体之间匹配的要求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/0a668373c056/cancers-14-03168-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/dc3c7c80255d/cancers-14-03168-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/4e6e086bf1d5/cancers-14-03168-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/ff5ea41008c4/cancers-14-03168-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/df74d8fc2bce/cancers-14-03168-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/0a668373c056/cancers-14-03168-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/dc3c7c80255d/cancers-14-03168-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/4e6e086bf1d5/cancers-14-03168-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/ff5ea41008c4/cancers-14-03168-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/df74d8fc2bce/cancers-14-03168-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/9264759/0a668373c056/cancers-14-03168-g005.jpg

相似文献

[1]
Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells.

Cancers (Basel). 2022-6-28

[2]
4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies.

Hum Gene Ther. 2010-1

[3]
Adjunct Therapy with T Regulatory Cells Decreases Inflammation and Preserves the Anti-Tumor Activity of CAR T Cells.

Cells. 2023-7-18

[4]
A novel TCR-like CAR with specificity for PR1/HLA-A2 effectively targets myeloid leukemia in vitro when expressed in human adult peripheral blood and cord blood T cells.

Cytotherapy. 2016-8

[5]
PR1-specific cytotoxic T lymphocytes are relatively frequent in umbilical cord blood and can be effectively expanded to target myeloid leukemia.

Cytotherapy. 2016-8

[6]
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Leukemia. 2020-12

[7]
IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia.

Leukemia. 2015-2

[8]
[Umbilical cord blood as a source of stem cells].

Acta Med Croatica. 2006-6

[9]
Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML.

Oncoimmunology. 2021

[10]
Ex vivo expansion, maturation, and activation of umbilical cord blood-derived T lymphocytes with IL-2, IL-12, anti-CD3, and IL-7. Potential for adoptive cellular immunotherapy post-umbilical cord blood transplantation.

Exp Hematol. 2002-3

引用本文的文献

[1]
Immune composition of the mononuclear cell fraction of human umbilical cord blood.

Front Immunol. 2025-8-1

[2]
Allogeneic CART progress: platforms, current progress and limitations.

Front Immunol. 2025-6-12

[3]
Case Report: CD19 CAR-T cells derived from recipient of umbilical cord blood transplantation effectively treated relapsed acute lymphoblastic leukemia after UCBT.

Front Immunol. 2025-5-19

[4]
White Light Spectroscopy Characteristics and Expansion Dynamic Behavior of Primary T-Cells: A Possibility of Online, Real-Time, and Sampling-Less CAR T-Cell Production Monitoring.

Biosensors (Basel). 2025-4-15

[5]
New player in CAR-T manufacture field: comparison of umbilical cord to peripheral blood strategies.

Front Immunol. 2025-3-21

[6]
Clinical development of allogeneic chimeric antigen receptor αβ-T cells.

Mol Ther. 2025-6-4

[7]
Restoring mitochondrial function promotes hematopoietic reconstitution from cord blood following cryopreservation-related functional decline.

J Clin Invest. 2025-3-4

[8]
Allogeneic and other innovative chimeric antigen receptor platforms.

Clin Hematol Int. 2024-9-27

[9]
Revolutionizing Cancer Treatments through Stem Cell-Derived CAR T Cells for Immunotherapy: Opening New Horizons for the Future of Oncology.

Cells. 2024-9-10

[10]
Advances in manufacturing chimeric antigen receptor immune cell therapies.

Semin Immunopathol. 2024-8-16

本文引用的文献

[1]
Decade-long leukaemia remissions with persistence of CD4 CAR T cells.

Nature. 2022-2

[2]
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Cancer Gene Ther. 2022-7

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Am Soc Clin Oncol Educ Book. 2021-3

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Leukemia. 2021-12

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Cancers (Basel). 2021-4-16

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Front Pediatr. 2020-10-2

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Next-Generation Manufacturing Protocols Enriching T CAR T Cells Can Overcome Disease-Specific T Cell Defects in Cancer Patients.

Front Immunol. 2020

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State of the art in CAR T cell therapy for CD19+ B cell malignancies.

J Clin Invest. 2020-4-1

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Memory T cells: strategies for optimizing tumor immunotherapy.

Protein Cell. 2020-8

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