CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response

被引：191

作者：

Kuhn, Nicholas F. ^{[1
,2
]}

Purdon, Terence J. ^{[2
]}

van Leeuwen, Dayenne G. ^{[2
]}

Lopez, Andrea, V ^{[2
]}

Curran, Kevin J. ^{[3
]}

Daniyan, Anthony F. ^{[2
]}

Brentjens, Renier J. ^{[2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA

来源：

CANCER CELL | 2019年 / 35卷 / 03期

基金：

美国国家卫生研究院;

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; DENDRITIC CELLS; B-CELLS; PHASE-I; EXPRESSION; ACTIVATION; CAR; MOUSE; IMMUNOTHERAPY; EFFICACY;

D O I：

10.1016/j.ccell.2019.02.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chimeric antigen receptor (CAR) T cells provide great efficacy in B cell malignancies. However, improved CAR T cell therapies are still needed. Here, we engineered tumor-targeted CAR T cells to constitutively express the immune-stimulatory molecule CD40 ligand (CD40L) and explored efficacy in differentmouse leukemia/ lymphoma models. We observed that CD40L(+) CAR T cells circumvent tumor immune escape via antigen loss through CD40/CD40L-mediated cytotoxicity and induction of a sustained, endogenous immune response. After adoptive cell transfer, the CD40L(+) CAR T cells displayed superior antitumor efficacy, licensed antigen-presenting cells, enhanced recruitment of immune effectors, and mobilized endogenous tumorrecognizing T cells. These effects were absent in Cd40(-/-) mice and provide a rationale for the use of CD40L(+) CAR T cells in cancer treatment.

引用

页码：473 / +

页数：22

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