In this study, we found that sSLAMF7 enhanced the growth of MM cells via homophilic interaction with surface SLAMF7 and subsequent activation of the SHP-2 and ERK signaling pathways.
Our study demonstrates that the immune receptor CD48 is overexpressed on MM cells together with SLAMF7, and that CD48 may be considered as an alternative target for treatment of MM in cases showing weak expression of SLAMF7.
Therapeutic monoclonal antibodies targeting SLAMF7 and CD38 are the first classes of targeted immunotherapies approved for multiple myeloma, a cancer of plasma cells.
However, cure of MM is still difficult, and several other targets, for example immunoglobulin kappa chain, SLAM Family Member 7 (SLAMF7), or G-protein coupled receptor family C group 5 member D (GPRC5D), are being tested as targets for CAR T cells.
Chimeric antigen receptor (CAR) engineered T cells targeting B cell maturation antigen (BCMA), CD138, CS1 glycoprotein antigen (SLAMF7) and light chains are in active development for therapy of refractory /relapsed (RR) MM.
Thus, biomarkers like disease burden, NK-cell count and SLAMF7 expression on myeloma cells may help to define myeloma patients with high likelihood to respond to elotuzumab treatment.
CD38 and SLAMF7 are the main surface molecules leading to the development of monoclonal antibodies (mAbs) recently approved for the treatment of relapsing MM patients.
Furthermore, the <i>JAK2</i>V617F allele burden of SLAMF7<sup>high</sup> monocytes was significantly higher than that of SLAMF7<sup>low</sup> monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma.
In addition, the anti-SLAMF7 antibody-mediated antibody-dependent cellular cytotoxicity of NK cells against MM cell lines was inhibited by recombinant SLAMF7 protein.
As of July 2017, antibodies clinically available in Japan for the treatment of multiple myeloma are elotuzumab against SLAMF7 and daratumumab against CD38.
Intravenous elotuzumab (Empliciti™), a monoclonal antibody targeting the signalling lymphocytic activation molecule F7 (SLAMF7) glycoprotein, is approved for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in previously-treated adult patients.
In this article, we comprehensively review the clinical pharmacology of elotuzumab, a first-in-class monoclonal anti-SLAMF7 antibody approved in combination with lenalidomide and dexamethasone (ELd) for the treatment of patients with MM and one to three prior therapies.
Elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7, which is highly expressed on myeloma cells, and the antibody is approved for the treatment of relapsed and/or refractory (RR) MM in combination with lenalidomide and dexamethasone.
The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM).
We confirmed uniform, high-level expression of SLAMF7 on malignant plasma cells in previously untreated and in relapsed/refractory (R/R) myeloma patients who had received previous treatment with proteasome inhibitors and immunomodulatory drugs.
Elotuzumab is a humanized monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7), approved by the US Food and Drug Administration (FDA) in 2015 and the European Medicines Agency in 2016 for the treatment of MM.
Elotuzumab is an immunostimulatory monoclonal antibody that binds to SLAMF7, a type-1 transmembrane protein expressed on myeloma and natural killer cells.
Elotuzumab is a humanized, immunostimulatory anti-signaling lymphocytic activation molecule F7 (SLAMF7) IgG1 monoclonal antibody indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma (MM) who have received 1-3 prior therapies.