Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells

被引：284

作者：

Kochenderfer, James N. ^{[1
]}

Yu, Zhiya ^{[1
]}

Frasheri, Dorina ^{[1
]}

Restifo, Nicholas P. ^{[1
]}

Rosenberg, Steven A. ^{[1
]}

机构：

[1] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA

来源：

BLOOD | 2010年 / 116卷 / 19期

基金：

美国国家卫生研究院;

关键词：

ANTITUMOR-ACTIVITY; IN-VIVO; ENHANCED SURVIVAL; REGULATORY-CELLS; IMMUNOTHERAPY; LYMPHOCYTES; ANTIBODY; EXPRESSION; GENE; EFFICACY;

D O I：

10.1182/blood-2010-01-265041

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. One infusion of anti-CD19-CAR-transduced T cells completely eliminated normal B cells from mice for at least 143 days. Anti-CD19- CAR-transduced T cells eradicated intraperitoneally injected lymphoma cells and large subcutaneous lymphoma masses. The antilymphoma efficacy of anti-CD19-CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19-CAR-transduced T-cell infusion. Anti-CD19-CAR- transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19-CAR-transduced T cells in a clinically relevant murine model. (Blood. 2010; 116(19):3875-3886)

引用

收藏

页码：3875 / 3886

页数：12

相关论文

共 52 条

[1] CD8+T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells [J].

Antony, PA ;

Piccirillo, CA ;

Akpinarli, A ;

Finkelstein, SE ;

Speiss, PJ ;

Surman, DR ;

Palmer, DC ;

Chan, CC ;

Klebanoff, CA ;

Overwijk, WW ;

Rosenberg, SA ;

Restifo, NP .

JOURNAL OF IMMUNOLOGY, 2005, 174 (05) :2591-2601

[2] Rapid specific amplification of rat antibody cDNA from nine hybridomas in the presence of myeloma light chains [J].

Brady, Jamie L. ;

Corbett, Alexandra J. ;

McKenzie, Brent S. ;

Lew, Andrew M. .

JOURNAL OF IMMUNOLOGICAL METHODS, 2006, 315 (1-2) :61-67

[3] Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15 [J].

Brentjens, RJ ;

Latouche, JB ;

Santos, E ;

Marti, F ;

Gong, MC ;

Lyddane, C ;

King, PD ;

Larson, S ;

Weiss, M ;

Rivière, I ;

Sadelain, M .

NATURE MEDICINE, 2003, 9 (03) :279-286

[4]

CAMPBELL MJ, 1988, J IMMUNOL, V141, P3227

[5] Natural Expression of the CD19 Antigen Impacts the Long-Term Engraftment but Not Antitumor Activity of CD19-Specific Engineered T Cells [J].

Cheadle, Eleanor J. ;

Hawkins, Robert E. ;

Batha, Hayley ;

O'Neill, Allison L. ;

Dovedi, Simon J. ;

Gilham, David E. .

JOURNAL OF IMMUNOLOGY, 2010, 184 (04) :1885-1896

[6] SURFACE-ANTIGEN EXPRESSION AND IMMUNOGLOBULIN GENE REARRANGEMENT DURING MOUSE PRE-B-CELL DEVELOPMENT [J].

COFFMAN, RL .

IMMUNOLOGICAL REVIEWS, 1983, 69 :5-23

[7] Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis [J].

Combadiere, B ;

Freedman, M ;

Chen, L ;

Shores, EW ;

Love, P ;

Lenardo, MJ .

JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (05) :2109-2117

[8] Adoptive Cell Therapy for Patients With Metastatic Melanoma: Evaluation of Intensive Myeloablative Chemoradiation Preparative Regimens [J].

Dudley, Mark E. ;

Yang, James C. ;

Sherry, Richard ;

Hughes, Marybeth S. ;

Royal, Richard ;

Kammula, Udai ;

Robbins, Paul F. ;

Huang, JianPing ;

Citrin, Deborah E. ;

Leitman, Susan F. ;

Wunderlich, John ;

Restifo, Nicholas P. ;

Thomasian, Armen ;

Downey, Stephanie G. ;

Smith, Franz O. ;

Klapper, Jacob ;

Morton, Kathleen ;

Laurencot, Carolyn ;

White, Donald E. ;

Rosenberg, Steven A. .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (32) :5233-5239

[9] Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells [J].

Gattinoni, L ;

Finkelstein, SE ;

Klebanoff, CA ;

Antony, PA ;

Palmer, DC ;

Spiess, PJ ;

Hwang, LN ;

Yu, ZY ;

Wrzesinski, C ;

Heimann, DM ;

Surh, CD ;

Rosenberg, SA ;

Restifo, NP .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (07) :907-912

[10] EXPRESSION OF IMMUNOGLOBULIN-T-CELL RECEPTOR CHIMERIC MOLECULES AS FUNCTIONAL RECEPTORS WITH ANTIBODY-TYPE SPECIFICITY [J].

GROSS, G ;

WAKS, T ;

ESHHAR, Z .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (24) :10024-10028

← 1 2 3 4 5 6 →