OX40 is a potent co-stimulatory 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 anti-tumor 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 12/30 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 anti-tumor reactivity of T and B cells in patients with melanoma. Our findings clinically validate OX40 as a potent immune-stimulating target for treatment in cancer patients, providing a generalizable tool to favorably influence the antitumor properties of circulating T cells, B cells and intratumoral regulatory T cells.

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Primary hyperparathyroidism (HPT) contributes to the onset of many chronic conditions. Although parathyroidectomy is the only definitive treatment, observation remains a valid option. Over a 3-year span, a major health plan was queried for HPT and benign parathyroid neoplasm. Patients with secondary and tertiary HPT, Stage III to V kidney disease, and prior renal transplant were excluded. Patients were divided into: observation (Group 1), parathyroidectomy during the study period (Group 2), and parathyroidectomy before the study group (Group 3), and were compared with a control group of 27,092 adult members without HPT using analysis of variance. The 3-year mean total allowed expenditure for Group One (n = 559), Group Two (n = 93), and Group Three (n = 48) were $21,267, $37,043, and $14,702, respectively. Groups One and Two had significantly higher use than the nonparathyroid group ( P < 0.0001), whereas that of Group Three was comparable. Group Two had the highest cost, whereas Group Three had a significantly lower cost than Group One ( P 0.0001). Primary hyperparathyroidism is associated with a higher use of healthcare resources. Patients observed incurred a higher allowed expenditure than those with prior parathyroidectomy. Surgical treatment may represent a cost-effective strategy for treatment of hyperparathyroidism, although more comprehensive studies are needed to confirm these findings.

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