CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges

被引:241
作者
Zhang, Xiaomin [1 ,2 ]
Zhu, Lingling [3 ]
Zhang, Hui [4 ]
Chen, Shanshan [3 ]
Xiao, Yang [2 ,5 ]
机构
[1] Guangzhou Univ Chinese Med, Dept Hematol, Jinshazhou Hosp, Guangzhou, Peoples R China
[2] Guangzhou Univ Chinese Med, Inst Clin Med Coll, Guangzhou, Peoples R China
[3] Southern Med Univ, Integrated Hosp Tradit Chinese Med, Canc Ctr, Guangzhou, Peoples R China
[4] Jishou Univ, Sch Med, Jishou, Peoples R China
[5] Shenzhen Qianhai Shekou Pilot Free Trade Zone Hosp, Dept Hematol, Shenzhen, Peoples R China
基金
中国国家自然科学基金;
关键词
CAR-T cell; hematological malignancies; CAR-T related toxicities; antigen escape; immunosuppressive tumor microenvironment; combinatorial therapy; CHIMERIC-ANTIGEN RECEPTOR; CYTOKINE RELEASE SYNDROME; HEMATOPOIETIC STEM-CELL; ACUTE MYELOID-LEUKEMIA; B-CELL; MULTIPLE-MYELOMA; HODGKIN LYMPHOMA; CD40; LIGAND; INFECTIOUS COMPLICATIONS; AXICABTAGENE CILOLEUCEL;
D O I
10.3389/fimmu.2022.927153
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-related coagulopathy. In addition, due to antigen escape, the limited CAR-T cell persistence, and immunosuppressive tumor microenvironment, a considerable proportion of patients relapse after CAR-T cell therapy. Thus, in this review, we focus on the progress and challenges of CAR-T cell therapy in hematological malignancies, such as attractive therapeutic targets, CAR-T related toxicities, and resistance to CAR-T cell therapy, and provide some practical recommendations.
引用
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页数:20
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共 268 条
[1]   Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study [J].
Abramson, Jeremy S. ;
Palomba, M. Lia ;
Gordon, Leo I. ;
Lunning, Matthew A. ;
Wang, Michael ;
Arnason, Jon ;
Mehta, Amitkumar ;
Purev, Enkhtsetseg ;
Maloney, David G. ;
Andreadis, Charalambos ;
Sehgal, Alison ;
Solomon, Scott R. ;
Ghosh, Nilanjan ;
Albertson, Tina M. ;
Garcia, Jacob ;
Kostic, Ana ;
Mallaney, Mary ;
Ogasawara, Ken ;
Newhall, Kathryn ;
Kim, Yeonhee ;
Li, Daniel ;
Siddiqi, Tanya .
LANCET, 2020, 396 (10254) :839-852
[2]   In Vivo Generation of CAR T Cells Selectively in Human CD4+ Lymphocytes [J].
Agarwal, Shiwani ;
Hanauer, Julia D. S. ;
Frank, Annika M. ;
Riechert, Vanessa ;
Thalheimer, Frederic B. ;
Buchholz, Christian J. .
MOLECULAR THERAPY, 2020, 28 (08) :1783-1794
[3]   γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes [J].
Airoldi, Irma ;
Bertaina, Alice ;
Prigione, Ignazia ;
Zorzoli, Alessia ;
Pagliara, Daria ;
Cocco, Claudia ;
Meazza, Raffaella ;
Loiacono, Fabrizio ;
Lucarelli, Barbarella ;
Bernardo, Maria Ester ;
Barbarito, Giulia ;
Pende, Daniela ;
Moretta, Alessandro ;
Pistoia, Vito ;
Moretta, Lorenzo ;
Locatelli, Franco .
BLOOD, 2015, 125 (15) :2349-2358
[4]   Armored BCMA CAR T Cells Eliminate Multiple Myeloma and Are Resistant to the Suppressive Effects of TGF-β [J].
Alabanza, Leah M. ;
Xiong, Ying ;
Vu, Bang ;
Webster, Brian ;
Wu, Darong ;
Hu, Peirong ;
Zhu, Zhongyu ;
Dropulic, Boro ;
Dash, Pradyot ;
Schneider, Dina .
FRONTIERS IN IMMUNOLOGY, 2022, 13
[5]   CD40L induces proliferation, self-renewal, rescue from apoptosis, and production of cytokines by CD40-expressing AML blasts [J].
Aldinucci, D ;
Poletto, D ;
Nanni, P ;
Degan, M ;
Rupolo, M ;
Pinto, A ;
Gattei, V .
EXPERIMENTAL HEMATOLOGY, 2002, 30 (11) :1283-1292
[6]   IL15 Enhances CAR-T Cell Antitumor Activity by Reducing mTORC1 Activity and Preserving Their Stem Cell Memory Phenotype [J].
Alizadeh, Darya ;
Wong, Robyn A. ;
Yang, Xin ;
Wang, Dongrui ;
Pecoraro, Joseph R. ;
Kuo, Cheng-Fu ;
Aguilar, Brenda ;
Qi, Yue ;
Ann, David K. ;
Starr, Renate ;
Urak, Ryan ;
Wang, Xiuli ;
Forman, Stephen J. ;
Brown, Christine E. .
CANCER IMMUNOLOGY RESEARCH, 2019, 7 (05) :759-772
[7]   Extracellular matrix and the myeloid-in-myeloma compartment: balancing tolerogenic and immunogenic inflammation in the myeloma niche [J].
Asimakopoulos, Fotis ;
Hope, Chelsea ;
Johnson, Michael G. ;
Pagenkopf, Adam ;
Gromek, Kimberly ;
Nagel, Bradley .
JOURNAL OF LEUKOCYTE BIOLOGY, 2017, 102 (02) :265-275
[8]   An orthogonal IL-2 and IL-2Rβ system drives persistence and activation of CART cells and clearance of bulky lymphoma [J].
Aspuria, Paul-Joseph ;
Vivona, Sandro ;
Bauer, Michele ;
Semana, Marie ;
Ratti, Navneet ;
McCauley, Scott ;
Riener, Romina ;
Malefyt, Rene de Waal ;
Rokkam, Deepti ;
Emmerich, Jan ;
Kastelein, Rob A. ;
Lupardus, Patrick J. ;
Oft, Martin .
SCIENCE TRANSLATIONAL MEDICINE, 2021, 13 (625)
[9]   Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma [J].
Atanackovic, Djordje ;
Panse, Jens ;
Hildebrandt, York ;
Jadczak, Adam ;
Kobold, Sebastian ;
Cao, Yanran ;
Templin, Julia ;
Meyer, Sabrina ;
Reinhard, Henrike ;
Bartels, Katrin ;
Lajmi, Nesrine ;
Zander, Axel R. ;
Marx, Andreas H. ;
Bokemeyer, Carsten ;
Kroeger, Nicolaus .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2011, 96 (10) :1512-1520
[10]   Clinical Impact of Immune Cells and Their Spatial Interactions in Diffuse Large B-Cell Lymphoma Microenvironment [J].
Autio, Matias ;
Leivonen, Suvi-Katri ;
Bruck, Oscar ;
Karjalainen-Lindsberg, Marja-Liisa ;
Pellinen, Teijo ;
Leppa, Sirpa .
CLINICAL CANCER RESEARCH, 2022, 28 (04) :781-792