Oncotarget

Research Perspectives:

Targeting GITR in cancer immunotherapy – there is no perfect knowledge

Diwakar Davar _ and Roberta Zappasodi

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Oncotarget. 2023; 14:614-621. https://doi.org/10.18632/oncotarget.28461

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Abstract

Diwakar Davar1,2 and Roberta Zappasodi3,4

1 Hillman Cancer Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15232, USA

2 University of Pittsburgh, Pittsburgh, PA 15232, USA

3 Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, NY 10065, USA

4 Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, NY 10065, USA

Correspondence to:

Diwakar Davar, email: [email protected]

Keywords: cancer; immunotherapy; programmed death-1 (PD-1); cytotoxic T-lymphocyte Antigen-4 (CTLA-4); glucocorticoid-induced TNFR-related protein (GITR)

Received: April 19, 2023     Accepted: June 05, 2023     Published: June 19, 2023

Copyright: © 2023 Davar and Zappasodi. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Glucocorticoid-induced TNFR-related protein (GITR) belongs to the TNFR superfamily (TNFRSF) and stimulates both the acquired and innate immunity. GITR is broadly expressed on immune cells, particularly regulatory T cells (Tregs) and natural killer (NK) cells. Given its potential to promote T effector function and impede Treg immune suppression, GITR is an attractive target for cancer immunotherapy. Preclinically, GITR agonists have demonstrated potent anti-tumor efficacy singly and in combination with a variety of agents, including PD-1 blockade. Multiple GITR agonists have been advanced into the clinic, although the experience with these agents has been disappointing. Recent mechanistic insights into the roles of antibody structure, valency, and Fc functionality in mediating anti-tumor efficacy may explain some of the apparent inconsistency or discordance between preclinical data and observed clinical efficacy.


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