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Cancer Res. 2013 Dec 15;73(24):7189-7198. doi: 10.1158/0008-5472.CAN-12-4174. Epub 2013 Oct 31.

OX40 is a potent immune-stimulating target in late-stage cancer patients.

Author information

1
Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, 4805 NE Glisan St. Portland, OR 97213.
2
Oregon Health and Science University, Vaccine and Gene Therapy Institute, Beaverton, OR 97006.
#
Contributed equally

Abstract

OX40 is a potent costimulatory receptor that can potentiate T-cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function, and survival of T cells. Preclinical studies have shown that OX40 agonists increase antitumor immunity and improve tumor-free survival. In this study, we performed a phase I clinical trial using a mouse monoclonal antibody (mAb) that agonizes human OX40 signaling in patients with advanced cancer. Patients treated with one course of the anti-OX40 mAb showed an acceptable toxicity profile and regression of at least one metastatic lesion in 12 of 30 patients. Mechanistically, this treatment increased T and B cell responses to reporter antigen immunizations, led to preferential upregulation of OX40 on CD4(+) FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, and increased the antitumor reactivity of T and B cells in patients with melanoma. Our findings clinically validate OX40 as a potent immune-stimulating target for treatment in patients with cancer, providing a generalizable tool to favorably influence the antitumor properties of circulating T cells, B cells, and intratumoral regulatory T cells.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01644968.

PMID:
24177180
PMCID:
PMC3922072
DOI:
10.1158/0008-5472.CAN-12-4174
[Indexed for MEDLINE]
Free PMC Article

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