To evaluate the safety and activity of the fully human glucocorticoid-induced TNF receptor-related protein agonist IgG1 monoclonal antibody BMS-986156 with or without nivolumab in patients with advanced solid tumors.
The aim of the study was to analyze the expression of monocyte chemoattractant protein-1, interleukin-6 (IL-6), tumor necrosis factor-α, inducible isoform of nitric oxide synthase (iNOS), cyclooxygenase-2, and osteopontin in vitro in two different tumor cell lines under hypoxia (pO<sub>2</sub>≈1.5 mmHg) and/or acidosis (pH=6.6) for up to 24 hours since hypoxia and acidosis are common characteristics of solid tumors.
A novel biopharmaceutical, consisting of the F8 mAb (specific to a splice isoform of fibronectin) simultaneously fused to both TNF and IL2, was found to react with the majority of solid tumors and hematologic malignancies in mouse and man, but not with healthy adult tissues.
Synergistic activity of SMAC mimetics together with death agonists TNFα or TRAIL occurred <i>in vitro</i>, whereas their antitumor effects were augmented when combined with radiation and chemotherapeutic agents that induce TNFα <i>in vivo</i> In addition, clinical trials testing SMAC mimetics as single agents or together with chemo- or radiation therapies in patients with HNSCC and solid tumors are summarized.
The poly-lactic acid microspheres (PLAM) with intratumoral cytokine release hold tremendous potential for the immunotherapy of breast cancer, and TNF-α antagonists may offer therapeutic potential in solid tumors.
Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a member of the TRAF family and is dysregulated in diseases, such as atheroma, lymphoma, and solid tumors, but the role of TRAF1 in gastric cancer remains unknown.
A20, also known as tumor necrosis factor-α (TNFα)-induced protein 3 (TNFAIP3), has been identified as a key regulator of cell survival in many solid tumors.
In recent years, several TNF alpha promoter polymorphisms have been identified and related to the expression level of cytokine and to the susceptibility to solid tumors.
TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: a phase I study in patients with solid tumors.