Multiple myelomas (MMs) are etiologically heterogeneous and there are limited treatment options; indeed, current
monoclonal antibody therapies have had limited success, so more effective
antibodies are urgently needed. Polyclonal
antibodies are a possible alternative because they target multiple
antigens simultaneously. In this study, we produced polyclonal rabbit anti-murine
plasmacytoma cell
immunoglobulin (PAb) by immunizing rabbits with the murine
plasmacytoma cell line MPC-11. The isolated PAb bound to plasma
surface antigens in several MM cell lines, inhibited their proliferation as revealed by MTT assay, and induce apoptosis as indicated by flow cytometry, microscopic observation of apoptotic changes in morphology, and DNA fragmentation on
agarose gels. The cytotoxicity of PAb on MPC-11 cell lines was both dose-dependent and time-dependent; PAb exerted a 50% inhibitory effect on MPC-11 cell viability at a concentration of 200 µg/ml in 48 h. Flow cytometry demonstrated that PAb treatment significantly increased the number of apoptotic cells (48.1%) compared with control
IgG (8.3%). Apoptosis triggered by PAb was confirmed by activation of
caspase-3, -8, and -9. Serial intravenous or
intraperitoneal injections of PAb inhibited tumour growth and prolonged survival in mice bearing murine
plasmacytoma, while TUNEL assay demonstrated that PAb induced statistically significant apoptosis (P < 0.05) compared to control treatments. We conclude that PAb is an effective agent for in vitro and in vivo induction of apoptosis in
multiple myeloma and that exploratory clinical trials may be warranted.