The Immune Revolution: A Case for Priming, Not Checkpoint

被引：242

作者：

Vonderheide, Robert H. ^{[1
]}

机构：

[1] Univ Penn, Abramson Canc Ctr, 12 Floor South Pavil,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA

来源：

CANCER CELL | 2018年 / 33卷 / 04期

关键词：

T-CELL IMMUNITY; MONOCLONAL-ANTIBODY CP-870,893; AGONIST CD40 ANTIBODY; HUMAN B-CELLS; DENDRITIC CELLS; PHASE-I; PANCREATIC-CANCER; MAMMARY-TUMORS; ANTI-CD40; THERAPY;

D O I：

10.1016/j.ccell.2018.03.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Most tumors are unresponsive to immune checkpoint blockade, especially if deep immunosuppression in the tumor develops prior to and prevents T cell immunosurveillance. Failed or frustrated T cell priming often needs repair before successful sensitization to PD-1/PD-L1 blockade. CD40 activation plays a critical role in generating T cell immunity, by activating dendritic cells, and converting cold tumors to hot. In preclinical studies, agonistic CD40 antibodies demonstrate T cell-dependent anti-tumor activity, especially in combination with chemotherapy, checkpoint inhibitory antibodies, and other immune modulators. With the advent of multiple CD40 agonists with acceptable single-agent toxicity, clinical evaluation of CD40 combinations has accelerated.

引用

页码：563 / 569

页数：7

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