A Monoclonal Antibody Specific for Free Human Kappa Light Chains Induces Apoptosis of Multiple Myeloma Cells and Exhibits Anti-Tumor Activity In Vivo.

Despite high dose chemotherapy and autologous stem cell transplant, multiple myeloma (MM) remains an incurable malignancy, with a median 5 year survival of less than 20%. With the exception of idiotype, few antigen targets have been identified that would facilitate specific immunotherapy of MM. We have previously described a murine monoclonal antibody that recognizes a conformation-dependent epitope on free human kappa light chains and a cell surface antigen, KMA, expressed on kappa MM plasma (MM_κ) cells (Raison, RL and Boux, HA Mol Immunol 1985 22:1393). Here we show that the murine antibody, designated mKap, bound specifically to a range of MM_κ cell lines and inhibited the in vitro growth of these cells. Flow cytometric analysis (Annexin-V and PI staining) of MM_κcell lines incubated with mKap demonstrated a dose dependent induction of apoptosis. Furthermore, the presence of activated caspases in mKap treated cells was detected using the CaspACE™ FITC-VAD-FMK reagent. The induction, by mKap, of apoptosis in MM_κ cells occured in the absence of cross-linking second antibody or effector cells. In vivo, anti-tumor activity by mKap was demonstrated in a SCID mouse tumor xenograft model. Tumor growth was measured by quantitation of secreted myeloma Ig over a period of 6 weeks. From week 4 onwards, significantly lower serum concentrations of myeloma Ig were detected in animal groups receiving 3.0, 1.5, 0.3 and 0.15 mg total mKap compared to the untreated control (P<0.005 at week 4; P<0.0001 at week 5). The tumor-restricted specificity of mKap, coupled with its ability to inhibit MM_κ cell growth in vitro and in vivo, suggests the potential use of either a chimeric or humanised version of this antibody, alone or in combination with chemotherapy, for the treatment of kappa MM.