| Description | CD70 is a ligand expressed on the surface of activated lymphocytes and mature dendritic cells that, in its binding to CD27 receptors, plays an important role in cell proliferation and survival. An overexpression of CD70 can result in the proliferation of malignant cells and has been documented in a variety of solid and hematological malignancies.[A241975] Cusatuzumab is a humanized IgG1 antibody targeted against CD70.[A241045] It is currently being investigated in the Phase 2 CULMINATE trial, in combination with [azacitidine], for the treatment of newly-diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in patients unsuitable for chemotherapy.[A241045,L39120] |
| Mechanism of Action | CD70 is transiently expressed on activated lymphocytes and mature dendritic cells, where it serves as a ligand for the CD27 receptor.[A241975] The CD70-CD27 interaction results in the downstream activation of the NF-B 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).[A241975] CD70 may also be involved in creating a tumor microenvironment that facilitates immune system evasion via the recruitment of regulatory T-cells.[A241975,A241045] 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.[L39120] In addition, cusatuzumab may exert some efficacy via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC).[L39120] |