Overcoming resistance to anti-CD19 CAR T-cell therapy in B-cell malignancies

被引：5

作者：

Yang, Xingcheng ^{[1
,2
]}

Wei, Jia ^{[1
,2
,3
]}

Zhou, Jianfeng ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Hematol, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China

[2] Immunotherapy Res Ctr Hematol Dis Hubei Prov, Wuhan, Hubei, Peoples R China

[3] Huazhong Univ Sci & Technol, Dept Hematol, Shanxi Bethune Hosp,Tongji Med Coll, Shanxi Acad Med Sci,Shanxi Med Univ,Shanxi Tongji, Taiyuan, Peoples R China

来源：

HEMATOLOGICAL ONCOLOGY | 2022年 / 40卷 / 05期

基金：

中国国家自然科学基金;

关键词：

antigen escape; B-cell malignancy; CD19; chimeric antigen receptor; overcoming strategy; resistance; T cell exhaustion; CHIMERIC-ANTIGEN-RECEPTOR; MYELOID CELLS; PERIPHERAL-BLOOD; LINEAGE SWITCH; TUMOR-IMMUNITY; LEUKEMIA; LYMPHOMA; EFFICACY; ESCAPE; EXPRESSION;

D O I：

10.1002/hon.3036

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has rapidly changed current treatment pattern, providing a better option for individuals with primary refractory or relapsed B-cell non-Hodgkin lymphoma (r/r B-NHL) and B-cell acute lymphoblastic leukemia (r/r B-ALL). However, despite the outstanding efficacy, a high relapse rate is still found in some B-cell malignancies after anti-CD19 CAR T-cell therapy, which emerges as a main barrier for improving the overall response and long-term outcomes. Understanding the resistance mechanism is crucial to improve current CAR T products, better incorporate them into the current therapy system and develop novel CAR approaches. Herein, we discuss the latest advances in understanding the mechanisms limiting efficacy of CAR T-cell therapy, resulting in CD19 negative (CD19(-)) and CD19 positive (CD19(+)) relapses. We also provide a whole scenario of current potential strategies to overcome these barriers.

引用

页码：821 / 834

页数：14

共 137 条

[1] IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor [J].

Adachi, Keishi ;

Kano, Yosuke ;

Nagai, Tomohiko ;

Okuyama, Namiko ;

Sakoda, Yukimi ;

Tamada, Koji .

NATURE BIOTECHNOLOGY, 2018, 36 (04) :346-+

[2] Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains [J].

Alabanza, Leah ;

Pegues, Melissa ;

Geldres, Claudia ;

Shi, Victoria ;

Wiltzius, Jed J. W. ;

Sievers, Stuart A. ;

Yang, Shicheng ;

Kochenderfer, James N. .

MOLECULAR THERAPY, 2017, 25 (11) :2452-2465

[3] 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

[4] Increased production of immature myeloid cells in cancer patients: A mechanism of immunosuppression in cancer [J].

Almand, B ;

Clark, JI ;

Nikitina, E ;

van Beynen, J ;

English, NR ;

Knight, SC ;

Carbone, DP ;

Gabrilovich, DI .

JOURNAL OF IMMUNOLOGY, 2001, 166 (01) :678-689

[5]

Ando Makoto, 2020, Immunol Med, V43, P1, DOI 10.1080/25785826.2019.1698261

[6]

[Anonymous], 2020, CANCER DISCOV, V10, P338, DOI 10.1158/2159-8290.CD-RW2020-017

[7] Phase I Study of a Bispecific Ligand-Directed Toxin Targeting CD22 and CD19 (DT2219) for Refractory B-cell Malignancies [J].

Bachanova, Veronika ;

Frankel, Arthur E. ;

Cao, Qing ;

Lewis, Dixie ;

Grzywacz, Bartosz ;

Verneris, Michael R. ;

Ustun, Celalettin ;

Lazaryan, Aleksandr ;

McClune, Brian ;

Warlick, Erica D. ;

Kantarjian, Hagop ;

Weisdorf, Daniel J. ;

Miller, Jeffrey S. ;

Vallera, Daniel A. .

CLINICAL CANCER RESEARCH, 2015, 21 (06) :1267-1272

[8] Induction of a central memory and stem cell memory phenotype in functionally active CD4+ and CD8+ CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19+ acute lymphoblastic leukemia [J].

Blaeschke, Franziska ;

Stenger, Dana ;

Kaeuferle, Theresa ;

Willier, Semjon ;

Lotfi, Ramin ;

Kaiser, Andrew Didier ;

Assenmacher, Mario ;

Doering, Michaela ;

Feucht, Judith ;

Feuchtinger, Tobias .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2018, 67 (07) :1053-1066

[9] 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

[10] Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma [J].

Brudno, Jennifer N. ;

Lam, Norris ;

Vanasse, Danielle ;

Shen, Yueh-wei ;

Rose, Jeremy J. ;

Rossi, John ;

Xue, Allen ;

Bot, Adrian ;

Scholler, Nathalie ;

Mikkilineni, Lekha ;

Roschewski, Mark ;

Dean, Robert ;

Cachau, Raul ;

Youkharibache, Philippe ;

Patel, Rashmika ;

Hansen, Brenna ;

Stroncek, David F. ;

Rosenberg, Steven A. ;

Gress, Ronald E. ;

Kochenderfer, James N. .

NATURE MEDICINE, 2020, 26 (02) :270-+

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