title: Polyclonal rabbit anti-murine plasmacytoma cell globulins induce myeloma cells apoptosis and inhibit tumour growth in mice.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital and School of Lifesciences, Sichuan University, Keyuan Road 4, Chengdu, Sichuan, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Mu
authors.forename: Jin-liang
authors.initials: JL
authors.lastname: Yang
authors.forename: Lan-tu
authors.initials: LT
authors.lastname: Gou
authors.forename: Yu-qin
authors.initials: YQ
authors.lastname: Yao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhi-hui
authors.initials: ZH
authors.lastname: Cheng
authors.forename: Hua-shan
authors.initials: HS
authors.lastname: Shi
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wen
authors.forename: Fei
authors.initials: F
authors.lastname: Leng
authors.forename: Feng-yu
authors.initials: FY
authors.lastname: Cui
authors.forename: Tian-Tai
authors.initials: TT
authors.lastname: Ma
authors.forename: Yu-quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D007136:Immunoglobulins / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000473:pathology*; D010954:Plasmacytoma / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits
chemical_list: D007136:Immunoglobulins