Hsi ED et al. - In a study to explore the therapeutic potential of HuLuc63 in multiple myeloma, it was shown that HuLuc63 eliminates myeloma cells, at least in part, via natural killer (NK)-mediated antibody-dependent cellular cytotoxicity (ADCC) and shows therapeutic potential of targeting CS1 with HuLuc63 for the treatment of multiple myeloma Methods
CS1 was analyzed by gene expression profiling and immunohistochemistry of multiple myeloma samples and numerous normal tissues
HuLuc63-mediated antimyeloma activity was tested in vitro in antibody-dependent cellular cytotoxicity (ADCC) assays and in vivo using the human OPM2 xenograft model in mice
Results
CS1 mRNA was expressed in >90% of 532 multiple myeloma cases, regardless of cytogenetic abnormalities
Anti-CS1 antibody staining of tissues showed strong staining of myeloma cells in all plasmacytomas and bone marrow biopsies
Flow cytometric analysis of pt samples using HuLuc63 showed specific staining of CD138+ myeloma cells, NK, NK-like T cells, and CD8+ T cells, with no binding detected on hematopoietic CD34+ stem cells
HuLuc63 exhibited significant in vitro ADCC using primary myeloma cells as targets and both allogeneic and autologous NK cells as effectors
HuLuc63 exerted significant in vivo antitumor activity, which depended on efficient Fc-CD16 interaction as well as presence of NK cells in the mice
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