The emerging landscape of novel 4-1BB (CD137) agonistic drugs for cancer immunotherapy

被引：63

作者：

Claus, Christina ^{[1
,2
]}

Ferrara-Koller, Claudia ^{[1
]}

Klein, Christian ^{[1
]}

机构：

[1] Roche Pharm Res & Early Dev pRED, Roche Innovat Ctr Zurich, Schlieren, Switzerland

[2] Roche Pharm Res & Early Dev pRED, Roche Innovat Ctr Zurich, Wagistr 10, CH-8952 Schlieren, Switzerland

来源：

MABS | 2023年 / 15卷 / 01期

关键词：

CD137; 4-1BB; TNFRSF9; cancer immunotherapy; costimulatory agonist; 4-1BB agonists; bispecific antibodies; PD-L1/4-1BB BISPECIFIC ANTIBODY; TYPE-1 DIABETES DEVELOPMENT; 1ST-IN-HUMAN PHASE-I; T-CELL-ACTIVATION; DOSE-ESCALATION; PRECLINICAL CHARACTERIZATION; CHECKPOINT INHIBITION; MONOCLONAL-ANTIBODIES; ANTITUMOR EFFICACY; CO-STIMULATION;

D O I：

10.1080/19420862.2023.2167189

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The clinical development of 4-1BB agonists for cancer immunotherapy has raised substantial interest during the past decade. The first generation of 4-1BB agonistic antibodies entering the clinic, urelumab (BMS-663513) and utomilumab (PF-05082566), failed due to (liver) toxicity or lack of efficacy, respectively. The two antibodies display differences in the affinity and the 4-1BB receptor epitope recognition, as well as the isotype, which determines the Fc-gamma-receptor (Fc gamma R) crosslinking activity. Based on this experience a very diverse landscape of second-generation 4-1BB agonists addressing the liabilities of first-generation agonists has recently been developed, with many entering clinical Phase 1 and 2 studies. This review provides an overview focusing on differences and their scientific rationale, as well as challenges foreseen during the clinical development of these molecules.

引用

页数：22

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