Tamura Hideto, Ishibashi Mariko, Takahashi Hidemi, Inokuchi Koiti
Department of Hematology, Nippon Medical School.
Department of Microbiology and Immunology, Nippon Medical School.
Rinsho Ketsueki. 2020;61(7):818-826. doi: 10.11406/rinketsu.61.818.
Reports have described the excellent efficacies of new immunotherapeutic strategies, such as monoclonal antibody (mAb) therapies, in multiple myeloma (MM) patients. Signaling lymphocytic activation molecule family (SLAMF) molecules are expressed strongly on normal lymphocytes and plasma cells from MM patients. The anti-SLAMF7 mAb elotuzumab (ELO) has been approved for the treatment of relapsed/refractory MM (RRMM). In MM patients, a high serum soluble SLAMF7 (sSLAMF7) concentration is associated with aggressive clinical characteristics. This suggests a proliferative function of the SLAMF7-sSLAMF7 interaction that could be inhibited by ELO. SLAMF3 is also expressed strongly and constitutively on myeloma cells. We observed the aggressive characteristics of SLAMF3 MM in vitro and in vivo. SLAMF3 interacts directly with the adaptor proteins SHP2 and GRB2. A gene expression analysis revealed that SLAMF3 transmits positive signals to MM cells via the MAPK/ERK signaling pathway and that sSLAMF3 levels are increased markedly in advanced MM. Thus, SLAMF3 may be a novel immunotherapeutic target in MM. SLAMF2 and SLAMF6 are also expressed strongly on MM cells, and the safety of antibody-drug conjugates that target these molecules in patients with RRMM is currently under study. Our and others' reports demonstrate the value of SLAMF molecules as promising new targets for antimyeloma immunotherapies.
报告描述了新的免疫治疗策略，如单克隆抗体（mAb）疗法，在多发性骨髓瘤（MM）患者中的卓越疗效。信号淋巴细胞激活分子家族（SLAMF）分子在MM患者的正常淋巴细胞和浆细胞上强烈表达。抗SLAMF7单克隆抗体埃罗妥珠单抗（ELO）已被批准用于治疗复发/难治性MM（RRMM）。在MM患者中，高血清可溶性SLAMF7（sSLAMF7）浓度与侵袭性临床特征相关。这表明SLAMF7-sSLAMF7相互作用的增殖功能可被ELO抑制。SLAMF3也在骨髓瘤细胞上强烈且组成性地表达。我们在体外和体内观察到SLAMF3 MM的侵袭性特征。SLAMF3直接与衔接蛋白SHP2和GRB2相互作用。基因表达分析显示，SLAMF3通过MAPK/ERK信号通路向MM细胞传递阳性信号，并且在晚期MM中sSLAMF3水平显著升高。因此，SLAMF3可能是MM中的一个新的免疫治疗靶点。SLAMF2和SLAMF6也在MM细胞上强烈表达，目前正在研究针对RRMM患者中这些分子的抗体药物偶联物的安全性。我们和其他人的报告证明了SLAMF分子作为抗骨髓瘤免疫治疗有前景的新靶点的价值。
