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

页码：3875 / 3886

页数：12

共 52 条

[11] EVALUATION OF HUMAN CARCINOEMBRYONIC-ANTIGEN (CEA)-TRANSDUCED AND NONTRANSDUCED MURINE TUMORS AS POTENTIAL TARGETS FOR ANTI-CEA THERAPIES [J].