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

BD Curti, M Kovacsovics-Bankowski, N Morris… - Cancer research, 2013 - AACR
BD Curti, M Kovacsovics-Bankowski, N Morris, E Walker, L Chisholm, K Floyd, J Walker
Cancer research, 2013AACR
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 …
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. Cancer Res; 73(24); 7189–98. ©2013 AACR.
AACR