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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Curti BD,Kovacsovics-Bankowski M,Morris N,Walker E,Chisholm L,Floyd K,Walker J,Gonzalez I,Meeuwsen T,Fox BA,Moudgil T,Miller W,Haley D,Coffey T,Fisher B,Delanty-Miller L,Rymarchyk N,Kelly T,Crocenzi T,Bernstein E,doi
10.1158/0008-5472.CAN-12-4174subject
Has Abstractpub_date
2013-12-15 00:00:00pages
7189-7198issue
24eissn
0008-5472issn
1538-7445journal_volume
73pub_type
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