Summary

Background

This non-therapeutic biosimilar antibody uses the same variable regions as the therapeutic antibody Elotuzumab, making it ideal for research use. Elotuzumab is a humanized monoclonal antibody that reacts with the cell surface glycoprotein CD319, which is commonly known as signaling lymphocytic activation molecule family member 7 (SLAMF7). SLAMF7 is highly expressed on myeloma cells, and in normal tissues, its expression is reported in natural killer (NK) cells, plasma cells, spleen cells, lymph nodes, peripheral blood leukocytes, bone marrow cells, etc. SLAMF7 is suggested to interact with SH2D1A, SH2D1B, PTPN6/SHP-1, PTPN11/SHP-2, INPP5D/SHIP1, CSK, and FYN proteins. Functionally, SLAMF7 is a self-ligand receptor of the SLAM family, and it is involved in the regulation and interconnection of both innate and adaptive immunity. Elotuzumab directly activates NK cells through both the SLAMF7 pathway and Fc receptor signaling. Elotuzumab also increases the expression of CD69 (on NK cells) and enhances IFN γ secretion and granzyme B biosynthesis, independent of Fc receptor signaling. In myeloma cells, based on in vitro studies, Elotuzumab is reported to target SLAMF7 and facilitate the interaction with NK cells for promoting myeloma cell death through the antibody-dependent cellular cytotoxicity (ADCC) mechanism. Elotuzumab disrupts the cell adhesion-mediated mechanisms of drug resistance in multiple myeloma cells by inhibiting their binding to bone marrow stromal cells in vitro . Elotuzumab is shown to reduce the growth of SLAMF7+ human multiple myeloma OPM2 xenografts in mice. Experiments involving in vitro as well as in vivo preclinical models demonstrated that a combination of Elotuzumab with the thalidomide derivative lenalidomide leads to enhanced activation of NK cells and increased anti-tumor activity.