Optimization of metabolism to improve efficacy during CAR-T cell manufacturing

被引：55

作者：

Zhang, Meng ^{[1
]}

Jin, Xin ^{[2
]}

Sun, Rui ^{[2
,3
]}

Xiong, Xia ^{[1
]}

Wang, Jiaxi ^{[1
]}

Xie, Danni ^{[1
]}

Zhao, MingFeng ^{[2
]}

机构：

[1] Tianjin Med Univ, Ctr Clin Coll 1, Tianjin 300192, Peoples R China

[2] Tianjin First Cent Hosp, Dept Hematol, Tianjin 300192, Peoples R China

[3] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2021年 / 19卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Metabolism; CAR-T; Immunotherapy; Glycolysis; OXPHOS; ACUTE LYMPHOBLASTIC-LEUKEMIA; MITOCHONDRIAL BIOGENESIS; TUMOR MICROENVIRONMENT; GLUCOSE-METABOLISM; AKT INHIBITION; MEMORY; CD8(+); EFFECTOR; ACTIVATION; DIFFERENTIATION;

D O I：

10.1186/s12967-021-03165-x

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Chimeric antigen receptor T cell (CAR-T cell) therapy is a relatively new, effective, and rapidly evolving therapeutic for adoptive immunotherapies. Although it has achieved remarkable effect in hematological malignancies, there are some problems that remain to be resolved. For example, there are high recurrence rates and poor efficacy in solid tumors. In this review, we first briefly describe the metabolic re-editing of T cells and the changes in metabolism during the preparation of CAR-T cells. Furthermore, we summarize the latest developments and newest strategies to improve the metabolic adaptability and antitumor activity of CAR-T cells in vitro and in vivo.

引用

页数：11

共 115 条

[1] Enhanced Therapeutic Efficacy and Memory of Tumor-Specific CD8 T Cells by Ex Vivo PI3K-δ Inhibition [J].

Abu Eid, Rasha ;

Ahmad, Shamim ;

Lin, Yuan ;

Webb, Mason ;

Berrong, Zuzana ;

Shrimali, Rajeev ;

Kumai, Takumi ;

Ananth, Sudha ;

Rodriguez, Paulo C. ;

Celis, Esteban ;

Janik, John ;

Mkrtichyan, Mikayel ;

Khleif, Samir N. .

CANCER RESEARCH, 2017, 77 (15) :4135-4145

[2] IL15 Enhances CAR-T Cell Antitumor Activity by Reducing mTORC1 Activity and Preserving Their Stem Cell Memory Phenotype [J].

Alizadeh, Darya ;

Wong, Robyn A. ;

Yang, Xin ;

Wang, Dongrui ;

Pecoraro, Joseph R. ;

Kuo, Cheng-Fu ;

Aguilar, Brenda ;

Qi, Yue ;

Ann, David K. ;

Starr, Renate ;

Urak, Ryan ;

Wang, Xiuli ;

Forman, Stephen J. ;

Brown, Christine E. .

CANCER IMMUNOLOGY RESEARCH, 2019, 7 (05) :759-772

[3] Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR-T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes [J].

Alsina, Melissa ;

Shah, Nina ;

Raje, Noopur S. ;

Jagannath, Sundar ;

Madduri, Deepu ;

Kaufman, Jonathan L. ;

Siegel, David S. ;

Munshi, Nikhil C. ;

Rosenblatt, Jacalyn ;

Lin, Yi ;

Jakubowiak, Andrzej ;

Jasielec, Jagoda ;

Timm, Alison ;

Turka, Ashley ;

Mao, Pingping ;

Martin, Nathan ;

Campbell, Timothy B. ;

Hege, Kristen ;

Bitter, Hans ;

Petrocca, Fabio ;

Berdeja, Jesus G. .

BLOOD, 2020, 136

[4] mTOR regulates memory CD8 T-cell differentiation [J].

Araki, Koichi ;

Turner, Alexandra P. ;

Shaffer, Virginia Oliva ;

Gangappa, Shivaprakash ;

Keller, Susanne A. ;

Bachmann, Martin F. ;

Larsen, Christian P. ;

Ahmed, Rafi .

NATURE, 2009, 460 (7251) :108-U124

[5]

Atkins RM., 2020, Blood, V136, P30, DOI DOI 10.1182/BLOOD-2020-143217

[6] The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse [J].

Baixauli, Francesc ;

Martin-Cofreces, Noa B. ;

Morlino, Giulia ;

Carrasco, Yolanda R. ;

Calabia-Linares, Carmen ;

Veiga, Esteban ;

Serrador, Juan M. ;

Sanchez-Madrid, Francisco .

EMBO JOURNAL, 2011, 30 (07) :1238-1250

[7] piggyBac™-Produced CAR-T Cells Exhibit Stem-Cell Memory Phenotype [J].

Barnett, Burton Earle ;

Hermanson, David L. ;

Smith, Jenessa Barbara ;

Wang, Xinxin ;

Tan, Yening ;

Martin, Christopher E. ;

Osertag, Eric M. ;

Shedlock, Devon J. .

BLOOD, 2016, 128 (22)

[8] Mesothelin-Specific Chimeric Antigen Receptor mRNA-Engineered T Cells Induce Antitumor Activity in Solid Malignancies [J].

Beatty, Gregory L. ;

Haas, Andrew R. ;

Maus, Marcela V. ;

Torigian, Drew A. ;

Soulen, Michael C. ;

Plesa, Gabriela ;

Chew, Anne ;

Zhao, Yangbing ;

Levine, Bruce L. ;

Albelda, Steven M. ;

Kalos, Michael ;

June, Carl H. .

CANCER IMMUNOLOGY RESEARCH, 2014, 2 (02) :112-120

[9] Pl3Kδ Inhibition Enhances the Antitumor Fitness of Adoptively Transferred CD8+ T Cells [J].

Bowers, Jacob S. ;

Majchrzak, Kinga ;

Nelson, Michelle H. ;

Aksoy, Bulent Arman ;

Wyatt, Megan M. ;

Smith, Aubrey S. ;

Bailey, Stefanie R. ;

Neal, Lillian R. ;

Hammerbacher, Jeffrey E. ;

Paulos, Chrystal M. .

FRONTIERS IN IMMUNOLOGY, 2017, 8

[10] Increasing AMPK Activity in Human T Cells Enhances Memory Subset Formation without Sacrificing in Vitro Expansion [J].

Braverman, Erica Lynne ;

Dobbs, Andrea ;

Monlish, Darlene A. ;

Byersdorfer, Craig .

BLOOD, 2020, 136

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