The Potential of CAR T Cell Therapy in Pancreatic Cancer

被引:100
作者
Akce, Mehmet [1 ]
Zaidi, Mohammad Y. [2 ,3 ]
Waller, Edmund K. [1 ]
El-Rayes, Bassel F. [1 ]
Lesinski, Gregory B. [1 ]
机构
[1] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Oncol, Atlanta, GA 30322 USA
[2] Indiana Univ, Dept Gen Surg, Bloomington, IN USA
[3] Emory Univ, Sch Med, Dept Surg, Div Surg Oncol, Atlanta, GA 30322 USA
来源
FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷
关键词
pancreas cancer; mesothelin; adoptive T cell therapy; CAR T cells; genetically engineered T cells; CHIMERIC-ANTIGEN-RECEPTOR; CARCINOEMBRYONIC ANTIGEN; ANTITUMOR-ACTIVITY; CYTOTOXIC LYMPHOCYTES; GENE-EXPRESSION; SERIAL ANALYSIS; MESOTHELIN; TARGET; IMMUNOTHERAPY; ANTIBODY;
D O I
10.3389/fimmu.2018.02166
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pancreatic cancer has a dismal prognosis and effective treatment options are limited. It is projected to be the second most common cause of cancer related mortality in the United States by 2030 and there is urgent unmet need for novel systemic treatment options. Immunotherapy with antibodies targeting PD-1, PD-L1, CTLA-4 has not shown clinical activity in unselected pancreatic cancer, emphasizing the need for combination immunotherapy approaches or other therapeutic strategies. As such, chimeric antigen receptor (CAR) T cell therapy represents an emerging therapeutic option for pancreatic cancer. This modality utilizes genetically engineered T cells that are redirected to specific cancer-associated antigens to elicit potent cytotoxic activity. This review summarizes the available preclinical data and highlights early phase clinical trials using CAR T cell approaches in pancreatic cancer, a disease state that is gaining attention as a conduit for cell therapy. Future directions in application of CAR T cell therapy are also considered including its ability to be directed against novel epitopes and combined with other therapeutic regimens.
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页数:11
相关论文
共 89 条
[1]   A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer [J].
Abate-Daga, Daniel ;
Lagisetty, Kiran H. ;
Tran, Eric ;
Zheng, Zhili ;
Gattinoni, Luca ;
Yu, Zhiya ;
Burns, William R. ;
Miermont, Anne M. ;
Teper, Yaroslav ;
Rudloff, Udo ;
Restifo, Nicholas P. ;
Feldman, Steven A. ;
Rosenberg, Steven A. ;
Morgan, Richard A. .
HUMAN GENE THERAPY, 2014, 25 (12) :1003-1012
[2]   Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes [J].
Abate-Daga, Daniel ;
Hanada, Ken-ichi ;
Davis, Jeremy L. ;
Yang, James C. ;
Rosenberg, Steven A. ;
Morgan, Richard A. .
BLOOD, 2013, 122 (08) :1399-1410
[3]   Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity [J].
Adusumilli, Prasad S. ;
Cherkassky, Leonid ;
Villena-Vargas, Jonathan ;
Colovos, Christos ;
Servais, Elliot ;
Plotkin, Jason ;
Jones, David R. ;
Sadelain, Michel .
SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (261)
[4]  
Argani P, 2001, CANCER RES, V61, P4320
[5]  
Argani P, 2001, CLIN CANCER RES, V7, P3862
[6]   Human CD26high T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence [J].
Bailey, Stefanie R. ;
Nelson, Michelle H. ;
Majchrzak, Kinga ;
Bowers, Jacob S. ;
Wyatt, Megan M. ;
Smith, Aubrey S. ;
Neal, Lillian R. ;
Shirai, Keisuke ;
Carpenito, Carmine ;
June, Carl H. ;
Zilliox, Michael J. ;
Paulos, Chrystal M. .
NATURE COMMUNICATIONS, 2017, 8
[7]   Inhibition of Interleukin-10 in the tumor microenvironment can restore mesothelin chimeric antigen receptor T cell activity in pancreatic cancer in vitro [J].
Batchu, Ramesh B. ;
Gruzdyn, Oksana V. ;
Mahmud, Ebrahem M. ;
Chukr, Fatme ;
Dachepalli, Rajesh ;
Manmari, Santosh K. ;
Mostafa, Gamal ;
Weaver, Donald W. ;
Gruber, Scott A. .
SURGERY, 2018, 163 (03) :627-632
[8]   Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial [J].
Beatty, Gregory L. ;
O'Hara, Mark H. ;
Lacey, Simon F. ;
Torigian, Drew A. ;
Nazimuddin, Farzana ;
Chen, Fang ;
Kulikovskaya, Irina M. ;
Soulen, Michael C. ;
McGarvey, Maureen ;
Nelson, Anne Marie ;
Gladney, Whitney L. ;
Levine, Bruce L. ;
Melenhorst, J. Joseph ;
Plesa, Gabriela ;
June, Carl H. .
GASTROENTEROLOGY, 2018, 155 (01) :29-32
[9]   Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma [J].
Beatty, Gregory L. .
ONCOIMMUNOLOGY, 2014, 3 (04)
[10]   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