Systemic Immune Response to a CD40-Agonist Antibody in Nonhuman Primates

J Leukoc Biol. 2024 Feb 19:qiae031. doi: 10.1093/jleuko/qiae031. Online ahead of print.ABSTRACTThe cell surface molecule CD40 is a member of the tumor necrosis factor receptor superfamily and is broadly expressed by immune cells including B cells, dendritic cells (DC), and monocytes, as well as other normal cells and some malignant cellsCD40 is constitutively expressed on antigen-presenting cells (APCs) and ligation promotes functional maturation leading to an increase in antigen presentation, cytokine production, and a subsequent increase in the activation of antigen specific T cells. It is postulated that CD40 agonists can mediate both T-cell-dependent and T-cell-independent immune mechanisms of tumor regression in mice and patients. In addition, it is believed that CD40 activation also promotes apoptotic death of tumor cells and that the presence of the molecule on the surface of cancer cells is an important factor in the generation of tumor-specific T-cell responses that contribute to tumor cell elimination. Notably, CD40-agonistic therapies were evaluated in patients with solid tumors and hematologic malignancies with reported success as a single agent. Preclinical studies have shown that subcutaneous administration of CD40-agonistic antibodies reduces systemic toxicity and elicits a stronger and localized pharmacodynamic response. Two independent studies in cynomolgus macaque (Macaca fascicularis) studies were performed to further evaluate, potentially immunotoxicologic...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Source Type: research