Challenges to Chimeric Antigen Receptor (CAR)-T Cell Therapy for Cancer

被引：1

作者：

Magee, Michael S. ^{[1
]}

Snook, Adam E. ^{[1
]}

机构：

[1] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA

来源：

DISCOVERY MEDICINE | 2014年 / 18卷 / 100期

关键词：

FIBROBLAST ACTIVATION PROTEIN; CD19-TARGETED T-CELLS; LYMPHOCYTES; SENSITIVITY; REMISSIONS; MALIGNANCY; TOXICITY; ABLATION; COLITIS; TUMORS;

D O I：

暂无

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 (CAR)expressing T cells have demonstrated potent clinical efficacy in patients with B cell malignancies. However, the use of CAR-T cell therapy targeting other cancers has, in part, been limited by both the induction of antigen-specific toxicities targeting normal tissues expressing the target-antigen, and the extreme potency of CAR-T cell treatments resulting in life-threatening cytokine-release syndromes. Herein, we discuss toxicities associated with CAR-T cell therapy in the clinic. Further, we discuss potential clinical interventions to ameliorate these toxicities and the application of preclinical animal models to predict the clinical utility of CAR-T cell therapy.

引用

页码：265 / 271

页数：7

共 47 条

[1] 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

[2] Suppression of Murine Colitis and its Associated Cancer by Carcinoembryonic Antigen-Specific Regulatory T Cells [J].

Blat, Dan ;

Zigmond, Ehud ;

Alteber, Zoya ;

Waks, Tova ;

Eshhar, Zelig .

MOLECULAR THERAPY, 2014, 22 (05) :1018-1028

[3] A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients [J].

Bleumer, I ;

Knuth, A ;

Oosterwijk, E ;

Hofmann, R ;

Varga, Z ;

Lamers, C ;

Kruit, W ;

Melchior, S ;

Mala, C ;

Ullrich, S ;

De Mulder, P ;

Mulders, PFA ;

Becks, J .

BRITISH JOURNAL OF CANCER, 2004, 90 (05) :985-990

[4] Balancing between Antitumor Efficacy and Autoimmune Pathology in T-Cell-Mediated Targeting of Carcinoembryonic Antigen [J].

Bos, Rinke ;

van Duikeren, Suzanne ;

Morreau, Hans ;

Franken, Kees ;

Schumacher, Ton N. M. ;

Haanen, John B. ;

van der Burg, Sjoerd H. ;

Melief, Cornelis J. M. ;

Offringa, Rienk .

CANCER RESEARCH, 2008, 68 (20) :8446-8455

[5] Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts [J].

Brentjens, Renier J. ;

Santos, Elmer ;

Nikhamin, Yan ;

Yeh, Raymond ;

Matsushita, Maiko ;

La Perle, Krista ;

Quintas-Cardama, Alfonso ;

Larson, Steven M. ;

Sadelain, Michel .

CLINICAL CANCER RESEARCH, 2007, 13 (18) :5426-5435

[6] Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias [J].

Brentjens, Renier J. ;

Riviere, Isabelle ;

Park, Jae H. ;

Davila, Marco L. ;

Wang, Xiuyan ;

Stefanski, Jolanta ;

Taylor, Clare ;

Yeh, Raymond ;

Bartido, Shirley ;

Borquez-Ojeda, Oriana ;

Olszewska, Malgorzata ;

Bernal, Yvette ;

Pegram, Hollie ;

Przybylowski, Mark ;

Hollyman, Daniel ;

Usachenko, Yelena ;

Pirraglia, Domenick ;

Hosey, James ;

Santos, Elmer ;

Halton, Elizabeth ;

Maslak, Peter ;

Scheinberg, David ;

Jurcic, Joseph ;

Heaney, Mark ;

Heller, Glenn ;

Frattini, Mark ;

Sadelain, Michel .

BLOOD, 2011, 118 (18) :4817-4828

[7] 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

[8] Novel mouse model for carcinoembryonic antigen-based therapy [J].

Chan, CHF ;

Stanners, CP .

MOLECULAR THERAPY, 2004, 9 (06) :775-785

[9] Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice [J].

Chinnasamy, Dhanalakshmi ;

Yu, Zhiya ;

Theoret, Marc R. ;

Zhao, Yangbing ;

Shrimali, Rajeev K. ;

Morgan, Richard A. ;

Feldman, Steven A. ;

Restifo, Nicholas P. ;

Rosenberg, Steven A. .

JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (11) :3953-3968

[10] T cells redirected by a CD3ζ chimeric antigen receptor can establish self-antigen-specific tumour protection in the long term [J].

Chmielewski, M. ;

Rappl, G. ;

Hombach, A. A. ;

Abken, H. .

GENE THERAPY, 2013, 20 (02) :177-186

← 1 2 3 4 5 →