Mouse Anti-Bovine CD4 Hybridoma [DD9]

Background Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disease affecting the skin and mucous membranes. Its pathogenic mechanism is still not fully understood. Regulatory T cells (Tregs) have been reported to play a significant role in regulating immune homeostasis in autoimmune disorders, such as PV. Aim To investigate the potential role of Tregs in the immunopathogenesis of PV. Methods We enrolled 15 patients with PV and 15 healthy controls (HCs). Peripheral blood samples were collected from all participants before treatment. This was followed by flow cytometric, real-time reverse transcription PCR, andin vitroinhibition-based functional assays to explore the immunopathogenesis of Tregs in PV. Results Our results showed no statistically significant differences in total CD4+CD25+ cells and CD4+CD25(high)cells. In addition, expression levels of FOXP3 mRNA and the corresponding FOXP3 protein remained unchanged in the patients with PV and the HCs. However, thein vitrosuppressive activity of CD4+CD25+ T cells was impaired in patients with PV compared with HCs. Conclusions Our observations suggest that inhibition of suppressive activity of Treg cells may be involved in the pathogenesis of PV.

Purpose: Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-inhuman study evaluated MEDI0562 in adults with advanced solid tumors. Patients and Methods: In this phase I, multicenter, open-label, single-arm, dose-escalation (3+3 design) study, patients received 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg MEDI0562 through intravenous infusion every 2 weeks, until confirmed disease progression or unacceptable toxicity. The primary objective evaluated safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics. Results: In total, 55 patients received =1 dose of MEDI0562 and were included in the analysis. The most common tumor type was squamous cell carcinoma of the head and neck (47%). Median duration of treatment was 10 weeks (range, 2-48 weeks). Treatment-related adverse events (TRAEs) occurred in 67% of patients, most commonly fatigue (31%) and infusion-related reactions (14%). Grade 3 TRAEs occurred in 14% of patients with no apparent dose relationship; no TRAEs resulted in death. Two patients had immune-related partial responses per protocol and 44% had stable disease. MEDI0562 induced increased Ki67+ CD4+ and CD8+ memory T-cell proliferation in the periphery and decreased intratumoral OX40+ FOXP3+ cells. Conclusions: MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pretreated patients. On-target pharmacodynamic effects were suggested in this setting. Further evaluation with immune checkpoint inhibitors is ongoing.