Cluster of Differentiation 27 (CD27) is a member of the Tumor Necrosis Factor Receptor superfamily and is integral to T-cell activation, providing a crucial costimulatory signal. When CD27 binds to its natural ligand, CD70, it enhances T-cell proliferation and the differentiation of effector and memory T cells. This interaction holds potential as an immune modulatory target for cancer treatment.
The CD27 agonistic antibody, varlilumab, has demonstrated promising efficacy in both hematological malignancies and solid tumors. Current research is focused on studying the combination therapy of varlilumab with PD-1 axis inhibitors, such as nivolumab or atezolizumab, which target immune checkpoint pathways.
Furthermore, CD70 expression is being explored as a therapeutic target for Antibody-Drug Conjugates (ADCs), antibodies that induce Antibody-Dependent Cellular Cytotoxicity (ADCC), as well as for chimeric antigen receptor (CAR) gene-modified T cells and specific dendritic cell vaccinations.
Clinical trials have shown that targeting the CD27 axis is feasible and safe, with the most common side effects being thrombocytopenia, fatigue, and nausea.
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