Science Gone Translational: the OX40 Agonist Story

Overview

Journal Immunol Rev

Specialties Allergy & Immunology
General Surgery

Date 2011 Oct 25

PMID 22017441

Citations 83

Authors

Andrew D Weinberg

Nicholas P Morris

Magdalena Kovacsovics-Bankowski

Walter J Urba

Brendan D Curti

Affiliations

Soon will be listed here.

Abstract

OX40 (CD134) is a tumor necrosis factor (TNF) receptor expressed primarily on activated CD4(+) and CD8(+) T cells and transmits a potent costimulatory signal when engaged. OX40 is transiently expressed after T-cell receptor engagement and is upregulated on the most recently antigen-activated T cells within inflammatory lesions (e.g. sites of autoimmune destruction and on tumor-infiltrating lymphocytes). Hence, it is an attractive target to modulate immune responses: OX40 blocking agents to inhibit undesirable inflammation or OX40 agonists to enhance immune responses. In regards to this review, OX40 agonists enhance anti-tumor immunity, which leads to therapeutic effects in mouse tumor models. A team of laboratory and clinical scientists at the Providence Cancer Center has collaborated to bring the preclinical observations in cancer models from the bench to the bedside. This review describes the journey from in vitro experiments through preclinical mouse models to the successful translation of the first OX40 agonist to the clinic for the treatment of patients with cancer.

Citing Articles

Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.

Sato A, Nagai H, Suzuki A, Ito A, Matsuyama S, Shibui N Front Immunol. 2025; 15:1473815.

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Tumor-infiltrating mast cells confer resistance to immunotherapy in pancreatic cancer.

Ma Y, Zhao X, Feng J, Qiu S, Ji B, Huang L iScience. 2024; 27(11):111085.

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Willoughby J, Dou L, Bhattacharya S, Jackson H, Seestaller-Wehr L, Kilian D J Immunother Cancer. 2024; 12(7).

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Plasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy.

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