Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy

被引：165

作者：

Abou-el-Enein, Mohamed ^{[1
,2
,3
,4
]}

Elsallab, Magdi ^{[3
,4
]}

Feldman, Steven A. ^{[5
]}

Fesnak, Andrew D. ^{[6
,7
]}

Heslop, Helen E. ^{[8
,9
]}

Marks, Peter ^{[10
]}

Till, Brian G. ^{[11
]}

Bauer, Gerhard ^{[12
]}

Savoldo, Barbara ^{[13
]}

机构：

[1] Univ Southern Calif, Keck Sch Med, Dept Med, Div Med Oncol, Los Angeles, CA 90033 USA

[2] Univ Southern Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90033 USA

[3] Univ Southern Calif, Joint USC CHLA Cell Therapy Program, Los Angeles, CA 90033 USA

[4] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

[5] Stanford Canc Inst, Stanford Ctr Canc Cell Therapy, Palo Alto, CA USA

[6] Univ Penn, Ctr Cellular Immunotherapies, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA

[8] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[9] Houston Methodist Hosp, Houston, TX 77030 USA

[10] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA

[11] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA

[12] Univ Calif Davis, Inst Regenerat Cures IRC, Sacramento, CA 95817 USA

[13] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

来源：

BLOOD CANCER DISCOVERY | 2021年 / 2卷 / 05期

关键词：

ADULT B-CELL; LENTIVIRAL VECTOR; GENE-THERAPY; ADOPTIVE IMMUNOTHERAPY; SLEEPING-BEAUTY; EXPANSION; TRANSDUCTION; MALIGNANCIES; REMISSIONS; GENERATION;

D O I：

10.1158/2643-3230.BCD-21-0084

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

As of April 2021, there are five commercially available chimeric antigen receptor (CAR) T cell therapies for hematologic malignancies. With the current transition of CAR T cell manufacturing from academia to industry, there is a shift toward Good Manufacturing Practice (GMP)-compliant closed and automated systems to ensure reproducibility and to meet the increased demand for patients with cancer. In this review, we describe current CART cell clinical manufacturing models and discuss emerging technologic advances that embrace scaling and production optimization. We summarize measures being used to shorten CART cell manufacturing times and highlight regulatory challenges to scaling production for clinical use. Significance: As the demand for CAR T cell cancer therapy increases, several closed and automated production platforms are being deployed, and others are in development. This review provides a critical appraisal of these technologies, which can be leveraged to scale and optimize the production of next-generation CAR T cells.

引用

页码：408 / 422

页数：15

共 144 条

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