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Review
. 2020 Jul;4(Suppl 3):e000733.
doi: 10.1136/esmoopen-2020-000733.

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

Iñaki Etxeberria  1 , Javier Glez-Vaz  2 , Álvaro Teijeira  2 , Ignacio Melero  3
Affiliations
Review

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

Iñaki Etxeberria et al. ESMO Open. 2020 Jul.

Abstract

CD137 (4-1BB) is a surface glycoprotein that belongs to the tumour necrosis factor receptor family (TNFRSF9). Its expression is induced on activation on a number of leucocyte types. Interestingly, for cancer immunotherapy, CD137 becomes expressed on primed T and natural killer (NK) cells, which on ligation provides powerful costimulatory signals. Perturbation of CD137 by CD137L or agonist monoclonal antibodies on activated CD8 T cells protects such antigen-specific cytotoxic T lymphocytes from apoptosis, enhances effector functionalities and favours persistence and memory differentiation. As a consequence, agonist antibodies exert potent antitumour effects in mouse models and the CD137 signalling domain is critical in chimeric antigen receptors (CAR) of CAR T cells approved to be used in the clinic. New formats of CD137 agonist moieties are being clinically developed, seeking potent costimulation targeted to the tumour microenvironment to avoid liver inflammation side effects, that have thus far limited and delayed clinical development.

Keywords: 4-1BB; CD137; cancer immunotherapy; mAb.

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Conflict of interest statement

Competing interests: IM is a paid consultant for Bristol-Myers Squibb, Roche, AstraZeneca, Pharmamar, Alligator, Numab, F-star, Servier, and MSD, and reports receiving commercial research grants from Alligator, Bristol-Myers Squibb, Roche, and Pharmamar.

Figures

Figure 1
Figure 1
Schematic representation of a tumour-infiltrating T lymphocyte expressing CD137 as a result of priming by tumour-antigen recognition. Then, novel strategies to make the most of CD137 costimulation are represented including bispecifics and direct intratumour injections. FAP, fibroblast activation protein; mAb, monoclonal antibody.
See this image and copyright information in PMC

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