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Cusatuzumab is a CD70-directed monoclonal antibody under investigation for the treatment of hematological malignancies.
Cusatuzumab is a CD70-directed monoclonal antibody under investigation for the treatment of hematological malignancies.
CD70 is transiently expressed on activated lymphocytes and mature dendritic cells, where it serves as a ligand for the CD27 receptor. The CD70-CD27 interaction results in the downstream activation of the NF-κB pathway responsible for cell proliferation and survival. The overexpression of CD70 can result in the proliferation of malignant cells and has been documented in a variety of solid and hematological tumors - elevated urinary concentrations of soluble CD27 (sCD27), a byproduct resulting from the CD70-CD27 interaction, are correlated with a poorer prognosis in patients with non-Hodgkin lymphoma (NHL), Waldenström macroglobulinemia, and acute lymphoblastic leukemia (ALL). CD70 may also be involved in creating a tumor microenvironment that facilitates immune system evasion via the recruitment of regulatory T-cells. Cusatuzumab is a humanized IgG1 monoclonal antibody targeted against CD70. In binding to CD70, cusatuzumab blocks the CD70-CD27 signaling that results in the proliferation of malignant cells and prevents the formation of sCD27. In addition, cusatuzumab may exert some efficacy via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC).
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