CAR-T cell manufacturing: Major process parameters and next-generation strategies

被引：89

作者：

Ayala Ceja, Melanie ^{[1
]}

Khericha, Mobina ^{[1
]}

Harris, Caitlin M. ^{[1
]}

Puig-Saus, Cristina ^{[2
,3
,4
]}

Chen, Yvonne Y. ^{[1
,3
,4
,5
]}

机构：

[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA

[3] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Parker Inst Canc Immunotherapy Ctr, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2024年 / 221卷 / 02期

关键词：

CENTRAL MEMORY; IN-VIVO; LISOCABTAGENE MARALEUCEL; HEMATOPOIETIC STEM; SLEEPING-BEAUTY; SITE SELECTION; RECEPTOR; THERAPY; CD8(+); CD4(+);

D O I：

10.1084/jem.20230903

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The success of CAR-T cell therapies is dependent on effective cell manufacturing that impacts product safety, efficacy, and patient accessibility. Here, we discuss major process parameters of autologous CAR-T cell manufacturing, regulatory considerations, and emerging technologies in therapeutic cell manufacturing. Chimeric antigen receptor (CAR)-T cell therapies have demonstrated strong curative potential and become a critical component in the array of B-cell malignancy treatments. Successful deployment of CAR-T cell therapies to treat hematologic and solid cancers, as well as other indications such as autoimmune diseases, is dependent on effective CAR-T cell manufacturing that impacts not only product safety and efficacy but also overall accessibility to patients in need. In this review, we discuss the major process parameters of autologous CAR-T cell manufacturing, as well as regulatory considerations and ongoing developments that will enable the next generation of CAR-T cell therapies.

引用

页数：14

共 156 条

[21]

Center for Biologics Evaluation and Research, 2022, FDA CBER OTAT Town Hall: Gene Therapy Chemistry, Manufacturing, and Controls

[22]

Center for Biologics Evaluation and Research, 2022, Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products: Draft Guidance for Industry

[23]

Center for Biologics Evaluation and Research, 2020, Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus during Product Manufacture and Patient Follow-Up

[24] Modified Manufacturing Process Modulates CD19CAR T-cell Engraftment Fitness and Leukemia-Free Survival in Pediatric and Young Adult Subjects [J].

Ceppi, Francesco ;

Wilson, Ashley L. ;

Annesley, Colleen ;

Kimmerly, Gabriella R. ;

Summers, Corinne ;

Brand, Adam ;

Seidel, Kristy ;

Wu, Qian Vicky ;

Beebe, Adam ;

Brown, Christopher ;

Mgebroff, Stephanie ;

Lindgren, Catherine ;

Rawlings-Rhea, Stephanie D. ;

Huang, Wenjun ;

Pulsipher, Michael A. ;

Wayne, Alan S. ;

Park, Julie R. ;

Jensen, Michael C. ;

Gardner, Rebecca A. .

CANCER IMMUNOLOGY RESEARCH, 2022, 10 (07) :856-870

[25] Molecular regulation of effector and memory T cell differentiation [J].

Chang, John T. ;

Wherry, E. John ;

Goldrath, Ananda W. .

NATURE IMMUNOLOGY, 2014, 15 (12) :1104-1115

[26] Value of Reducing Wait Times for Chimeric Antigen Receptor T-Cell Treatment: Evidence From Randomized Controlled Trial Data on Tisagenlecleucel for Diffuse Large B-Cell Lymphoma [J].

Chen, Alice J. ;

Zhang, Jie ;

Agarwal, Abhijit ;

Lakdawalla, Darius N. .

VALUE IN HEALTH, 2022, 25 (08) :1344-1351

[27] Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy [J].

Chen, Gregory M. ;

Chen, Changya ;

Das, Rajat K. ;

Gao, Peng ;

Chen, Chia-Hui ;

Bandyopadhyay, Shovik ;

Ding, Yang-Yang ;

Uzun, Yasin ;

Yu, Wenbao ;

Zhu, Qin ;

Myers, Regina M. ;

Grupp, Stephan A. ;

Barrett, David M. ;

Tan, Kai .

CANCER DISCOVERY, 2021, 11 (09) :2186-2199

[28] Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells [J].

Cheung, Alexander S. ;

Zhang, David K. Y. ;

Koshy, Sandeep T. ;

Mooney, David J. .

NATURE BIOTECHNOLOGY, 2018, 36 (02) :160-+

[29] CAR T cell viability release testing and clinical outcomes: is there a lower limit? [J].

Chong, Elise A. ;

Levine, Bruce L. ;

Grupp, Stephan A. ;

Davis, Megan M. ;

Siegel, Don L. ;

Maude, Shannon L. ;

Gladney, Whitney L. ;

Frey, Noelle V. ;

Porter, David L. ;

Hwang, Wei-Ting ;

Chong, Emeline R. ;

June, Carl H. ;

Schuster, Stephen J. .

BLOOD, 2019, 134 (21) :1873-1875

[30] Regulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy [J].

Colombo, Mario P. ;

Piconese, Silvia .

NATURE REVIEWS CANCER, 2007, 7 (11) :880-887

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