Immunotherapy in nude mice of human hepatoma using monoclonal antibodies against hepatitis B virus.
Immunotherapy in nude mice of human hepatoma using monoclonal antibodies against hepatitis B virus.
复制标题
使用抗乙型肝炎病毒单克隆抗体对人肝癌裸鼠进行免疫治疗。
作者：
Shouval,D;Shafritz,DA;ZurawskiJr,VR;Isselbacher,KJ;Wands,JR
人肝癌细胞系PLC/PRF/5含有整合的B型肝炎病毒DNA，合成并分泌B型肝炎病毒表面抗原（HBsAg）1，2。当注射到BALB/c裸鼠中时，这些细胞在几乎100%的动物中产生血管化良好的包裹肿瘤1。使用免疫荧光技术已证明PLC/PRF/5细胞表面和细胞质中存在HBsAg 1，3-5。最近，我们报道了HBsAg的单克隆抗体（IgG 1、IgG 2a和IgM同种型）与培养物中PLC/PRF/5细胞的HBsAg相关病毒决定簇结合，并使分泌到生长培养基中的HBsAg免疫沉淀6。另外，抗HBsAg的IgG 2a和IgM抗体（抗-HBs）在补体存在下在培养物中产生PLC/PRF/5细胞的特异性裂解，但对不表达HBsAg 6的人肝癌细胞没有裂解作用。在本研究中，我们证明，IgM和IgG 2a，但不是IgG 1，单克隆抗-HBs特异性地防止或抑制肿瘤形成在大量的无胸腺裸鼠注射PLC/PRF/5细胞。
The human hepatoma cell line PLC/PRF/5, which contains integrated hepatitis B virus DNA, synthesises and secretes hepatitis B virus surface antigen (HBsAg)1,2. When injected into BALB/c nude mice, these cells produce well-vascularized, encapsulated tumours in almost 100% of animals1. HBsAg has been demonstrated on the surface and in the cytoplasm of PLC/PRF/5 cells using immunofluorescence techniques1,3–5. Recently, we reported that monoclonal antibodies to HBsAg (IgG1, IgG2a and IgM isotypes) bind to HBsAg-associated viral determinants of PLC/PRF/5 cells in culture and immunoprecipitate HBsAg secreted into the growth medium6. Also IgG2a and IgM antibodies to HBsAg (anti-HBs) produce specific lysis of PLC/PRF/5 cells in culture in the presence of complement, but have no lytic effect on human hepatoma cells which do not express HBsAg6. In the present study, we demonstrate that IgM and IgG2a, but not IgG1, monoclonal anti-HBs specifically prevent or suppress tumour formation in a substantial number of athymic nude mice injected with PLC/PRF/5 cells.