The promise and challenges of immune agonist antibody development in cancer

被引：294

作者：

Mayes, Patrick A. ^{[1
,2
]}

Hance, Kenneth W. ^{[1
]}

Hoos, Axel ^{[1
]}

机构：

[1] GlaxoSmithKline, Oncol R&D, Collegeville, PA 19426 USA

[2] Incyte, Wilmington, DE USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2018年 / 17卷 / 07期

关键词：

REGULATORY T-CELLS; FC-GAMMA RECEPTORS; NECROSIS-FACTOR SUPERFAMILY; ANTI-CD40; MONOCLONAL-ANTIBODY; CD28 SUPERAGONIST TGN1412; ADVANCED SOLID TUMORS; LONG-TERM SURVIVAL; IMMUNOLOGICAL SYNAPSE; CRYSTAL-STRUCTURE; STRUCTURAL BASIS;

D O I：

10.1038/nrd.2018.75

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Immune cell functions are regulated by co-inhibitory and co-stimulatory receptors. The first two generations of cancer immunotherapy agents consist primarily of antagonist antibodies that block negative immune checkpoints, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte protein 4 (CTLA4). Looking ahead, there is substantial promise in targeting co-stimulatory receptors with agonist antibodies, and a growing number of these agents are making their way through various stages of development. This Review discusses the key considerations and potential pitfalls of immune agonist antibody design and development, their differentiating features from antagonist antibodies and the landscape of agonist antibodies in clinical development for cancer treatment.

引用

页码：509 / 527

页数：19

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