Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

被引：1036

作者：

Kochenderfer, James N. ^{[1
,2
]}

Wilson, Wyndham H. ^{[3
]}

Janik, John E. ^{[3
]}

Dudley, Mark E. ^{[2
]}

Stetler-Stevenson, Maryalice ^{[4
]}

Feldman, Steven A. ^{[2
]}

Maric, Irina ^{[1
]}

Raffeld, Mark ^{[4
]}

Nathan, Debbie-Ann N. ^{[2
]}

Lanier, Brock J. ^{[2
]}

Morgan, Richard A. ^{[2
]}

Rosenberg, Steven A. ^{[2
]}

机构：

[1] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA

[2] NCI, Surg Branch, Bethesda, MD 20892 USA

[3] NCI, Metab Branch, Bethesda, MD 20892 USA

[4] NCI, Pathol Lab, Bethesda, MD 20892 USA

来源：

BLOOD | 2010年 / 116卷 / 20期

基金：

美国国家卫生研究院;

关键词：

CHIMERIC ANTIGEN RECEPTOR; HUMAN BONE-MARROW; IN-VIVO; ADOPTIVE IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; LYMPHOCYTES; ANTIBODY; DIFFERENTIATION; PERSISTENCE; EFFICACY;

D O I：

10.1182/blood-2010-04-281931

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti-CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti-CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326. (Blood.2010;116(20):4099-4102)

引用

页码：4099 / 4102

页数：4

共 25 条

[21] The promise and potential pitfalls of chimeric antigen receptors
Sadelain, Michel
Brentjens, Renier
Riviere, Isabelle
[J]. CURRENT OPINION IN IMMUNOLOGY, 2009, 21 (02) : 215 - 223
[22] Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells
Till, Brian G.
Jensen, Michael C.
Wang, Jinjuan
Chen, Eric Y.
Wood, Brent L.
Greisman, Harvey A.
Qian, Xiaojun
James, Scott E.
Raubitschek, Andrew
Forman, Stephen J.
Gopal, Ajay K.
Pagel, John M.
Lindgren, Catherine G.
Greenberg, Philip D.
Riddell, Stanley R.
Press, Oliver W.
[J]. BLOOD, 2008, 112 (06) : 2261 - 2271
[23] UCKUN FM, 1988, BLOOD, V71, P13
[24] Immunophenotypic differentiation patterns of normal Hematopoiesis in human bone marrow: Reference patterns for age-related changes and disease-induced shifts
van Lochem, EG
van der Velden, VHJ
Wind, HK
te Marvelde, JG
Westerdaal, NAC
van Dongen, JM
[J]. CYTOMETRY PART B-CLINICAL CYTOMETRY, 2004, 60B (01) : 1 - 13
[25] Immunotherapy of Human Cancers Using Gene Modified T Lymphocytes
Vera, Juan F.
Brenner, Malcolm K.
Dotti, Gianpietro
[J]. CURRENT GENE THERAPY, 2009, 9 (05) : 396 - 408

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