OX40 Is a Potent Immune-Stimulating Target in Late-Stage Cancer Patients

被引：395

作者：

Curti, Brendan D. ^{[1
]}

Kovacsovics-Bankowski, Magdalena ^{[1
]}

Morris, Nicholas ^{[1
]}

Walker, Edwin ^{[1
]}

Chisholm, Lana ^{[1
]}

Floyd, Kevin ^{[1
]}

Walker, Joshua ^{[2
]}

Gonzalez, Iliana ^{[1
]}

Meeuwsen, Tanisha ^{[1
]}

Fox, Bernard A. ^{[1
]}

Moudgil, Tarsem ^{[1
]}

Miller, William ^{[1
]}

Haley, Daniel ^{[1
]}

Coffey, Todd ^{[1
]}

Fisher, Brenda ^{[1
]}

Delanty-Miller, Laurie ^{[1
]}

Rymarchyk, Nicole ^{[1
]}

Kelly, Tracy ^{[1
]}

Crocenzi, Todd ^{[1
]}

Bernstein, Eric ^{[1
]}

Sanborn, Rachel ^{[1
]}

Urba, Walter J. ^{[1
]}

Weinberg, Andrew D. ^{[1
]}

机构：

[1] Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA

[2] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA

来源：

CANCER RESEARCH | 2013年 / 73卷 / 24期

关键词：

T-CELL RESPONSES; POLYCHROMATIC FLOW-CYTOMETRY; REGULATORY T; IN-VIVO; PHASE-I; RECEPTOR; BLOCKADE; ANTIBODY; MEMORY; EFFECTOR;

D O I：

10.1158/0008-5472.CAN-12-4174

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2013 AACR.

引用

页码：7189 / 7198

页数：10

共 37 条

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[Anonymous], [No title captured]

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