Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety-A Systematic Review with Meta-Analysis

被引:67
作者
Yu, Wen-Liang [1 ,2 ]
Hua, Zi-Chun [2 ,3 ,4 ]
机构
[1] Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Ave Wai Long, Taipa 999078, Macao, Peoples R China
[2] Nanjing Univ, Changzhou High Tech Res Inst, Jiangsu Target Pharma Labs Inc, Changzhou 213164, Peoples R China
[3] Nanjing Univ, Sch Life Sci, Nanjing 210023, Jiangsu, Peoples R China
[4] Nanjing Univ, Shenzhen Res Inst, Shenzhen 518057, Peoples R China
关键词
chimeric antigen receptor T cell; response; side effect; relapse; subgroup analysis; meta-analysis; meta-regression analysis; CYTOKINE RELEASE SYNDROME; ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL; ANTITUMOR-ACTIVITY; INDUCE REMISSION; CANCER; IMMUNOTHERAPY; LYMPHOMA; TRIAL; PERSISTENCE;
D O I
10.3390/cancers11010047
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chimeric antigen receptors T cells (CAR T) had been used for treating various tumor patients in clinic, and owned an incredible efficacy in part of malignancies. However, CAR T therapy remains controversial due to doubts about its efficacy and safety in the clinical treatment of various malignancies. A total of 997 tumor patients from 52 studies were included in this review. Eligible studies were searched and reviewed from the databases of PubMed, Web of Science, Wanfang and Clinicaltrials.gov. Then meta-analysis and subgroup analysis were used to investigate the overall response rate (ORR), complete response rate (CRR), common side effect rate (CSER) and relapse rate (RR) of CAR T therapy for patients in clinical researches, respectively. The results further confirmed that CAR T therapy had a higher response rate for hematologic malignancies. More importantly, CAR T therapy had a higher CSER in patients with hematologic malignancies, and it had a similar RR in patients with different malignancies. Cell cultured without the addition of IL-2 and total administration less than 10(8) cells were recommended. This study offers a reference for future research regarding the application in solid and hematologic malignancies, side effects and relapse, and even the production processes of CAR T cells.
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页数:27
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共 69 条
[1]   Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma [J].
Ahmed, Nabil ;
Brawley, Vita S. ;
Hegde, Meenakshi ;
Robertson, Catherine ;
Ghazi, Alexia ;
Gerken, Claudia ;
Liu, Enli ;
Dakhova, Olga ;
Ashoori, Aidin ;
Corder, Amanda ;
Gray, Tara ;
Wu, Meng-Fen ;
Liu, Hao ;
Hicks, John ;
Rainusso, Nino ;
Dotti, Gianpietro ;
Mei, Zhuyong ;
Grilley, Bambi ;
Gee, Adrian ;
Rooney, Cliona M. ;
Brenner, Malcolm K. ;
Heslop, Helen E. ;
Wels, Winfried S. ;
Wang, Lisa L. ;
Anderson, Peter ;
Gottschalk, Stephen .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (15) :1688-+
[2]   T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma [J].
Ali, Syed Abbas ;
Shi, Victoria ;
Maric, Irina ;
Wang, Michael ;
Stroncek, David F. ;
Rose, Jeremy J. ;
Brudno, Jennifer N. ;
Stetler-Stevenson, Maryalice ;
Feldman, Steven A. ;
Hansen, Brenna G. ;
Fellowes, Vicki S. ;
Hakim, Frances T. ;
Gress, Ronald E. ;
Kochenderfer, James N. .
BLOOD, 2016, 128 (13) :1688-1700
[3]   Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells [J].
Allegra, Alessandro ;
Innao, Vanessa ;
Gerace, Demetrio ;
Vaddinelli, Doriana ;
Musolino, Caterina .
BLOOD CELLS MOLECULES AND DISEASES, 2016, 62 :49-63
[4]   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
[5]   Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy [J].
Brown, Christine E. ;
Alizadeh, Darya ;
Starr, Renate ;
Weng, Lihong ;
Wagner, Jamie R. ;
Naranjo, Araceli ;
Ostberg, Julie R. ;
Blanchard, M. Suzette ;
Kilpatrick, Julie ;
Simpson, Jennifer ;
Kurien, Anita ;
Priceman, Saul J. ;
Wang, Xiuli ;
Harshbarger, Todd L. ;
D'Apuzzo, Massimo ;
Ressler, Julie A. ;
Jensen, Michael C. ;
Barish, Michael E. ;
Chen, Mike ;
Portnow, Jana ;
Forman, Stephen J. ;
Badie, Behnam .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (26) :2561-2569
[6]   Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma [J].
Brown, Christine E. ;
Badie, Behnam ;
Barish, Michael E. ;
Weng, Lihong ;
Ostberg, Julie R. ;
Chang, Wen-Chung ;
Naranjo, Araceli ;
Starr, Renate ;
Wagner, Jamie ;
Wright, Christine ;
Zhai, Yubo ;
Bading, James R. ;
Ressler, Julie A. ;
Portnow, Jana ;
D'Apuzzo, Massimo ;
Forman, Stephen J. ;
Jensen, Michael C. .
CLINICAL CANCER RESEARCH, 2015, 21 (18) :4062-4072
[7]   CAR T-Cell Therapy Pediatric patients with relapsed and refractory acute lymphoblastic leukemia [J].
Callahan, Colleen ;
Baniewicz, Diane ;
Ely, Beth .
CLINICAL JOURNAL OF ONCOLOGY NURSING, 2017, 21 (02) :22-28
[8]   Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains [J].
Carpenito, Carmine ;
Milone, Michael C. ;
Hassan, Raffit ;
Simonet, Jacqueline C. ;
Lakhal, Mehdi ;
Suhoski, Megan M. ;
Varela-Rohena, Angel ;
Haines, Kathleen M. ;
Heitjan, Daniel F. ;
Albelda, Steven M. ;
Carroll, Richard G. ;
Riley, James L. ;
Pastan, Ira ;
June, Carl H. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (09) :3360-3365
[9]   Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation [J].
Chen, Yuhong ;
Cheng, Yifei ;
Suo, Pan ;
Yan, Chenhua ;
Wang, Yu ;
Chen, Yao ;
Han, Wei ;
Xu, Lanping ;
Zhang, Xiaohui ;
Liu, Kaiyan ;
Chang, Lungji ;
Xiao, Lei ;
Huang, Xiaojun .
BRITISH JOURNAL OF HAEMATOLOGY, 2017, 179 (04) :598-605
[10]   Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study [J].
Cruz, Conrad Russell Y. ;
Micklethwaite, Kenneth P. ;
Savoldo, Barbara ;
Ramos, Carlos A. ;
Lam, Sharon ;
Ku, Stephanie ;
Diouf, Oumar ;
Liu, Enli ;
Barrett, A. John ;
Ito, Sawa ;
Shpall, Elizabeth J. ;
Krance, Robert A. ;
Kamble, Rammurti T. ;
Carrum, George ;
Hosing, Chitra M. ;
Gee, Adrian P. ;
Mei, Zhuyong ;
Grilley, Bambi J. ;
Heslop, Helen E. ;
Rooney, Cliona M. ;
Brenner, Malcolm K. ;
Bollard, Catherine M. ;
Dotti, Gianpietro .
BLOOD, 2013, 122 (17) :2965-2973