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

ABSTRACT: 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 (FcγR) 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.

SUBMITTER: Claus C

PROVIDER: S-EPMC9897756 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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

Claus Christina C Ferrara-Koller Claudia C Klein Christian C

mAbs 20230101 1

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 (FcγR) crosslinking acti ...[more]

PMID: 36727218

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New emerging targets in cancer immunotherapy: CD137/4-1BB costimulatory axis.

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