Novel cancer therapy using human monoclonal antibody against human epidermal growth factor receptor

通过一次融合实验，获得了两株分泌抗A431细胞表皮生长因子受体(EGFR)单抗的小鼠杂交瘤细胞株，其中12-93Ig G可抑制[IL-EGF]与A431细胞的结合达95%以上。另一种抗体10-77IgM对EGF与A431细胞的结合无影响。这两种抗体都能免疫抑制A431膜Triton X-100提取液中的EGFR。在体外和体内抑制EGF与其受体的结合，对对纳米浓度的EGF表现相反生长反应的鳞状细胞癌细胞和涎腺腺癌细胞具有内在的促生长活性。此外，用12-93免疫组织化学方法检测了正常口腔粘膜、鳞癌、正常涎腺和涎腺肿瘤中EGFR的表达。我们发现抑制EGF结合的单抗在无血清培养条件下抑制口腔鳞癌细胞和涎腺来源的腺癌细胞的生长。此外，它还能抑制裸鼠体内移植的肿瘤的形成。受体抗体体内杀伤细胞的机制以及受体抗体对正常细胞可能的毒性作用有待进一步研究。然而，到目前为止，所获得的结果是令人鼓舞的，并表明针对生长因子、激素和转运蛋白受体的单抗最终可能被证明是可行的治疗剂。这种方法是产生肿瘤特异性单抗的一种可行的替代方法。

Two mouse hybridomas secreting monoclonal immunoglobulin g and m antibodies to epidermal growth factor receptors(EGFR)of A431 cells were obtained from one fusion experiment.One of the antibodies, 12-93 IgG inhibited the binding of[il-EGF to A431 cells by at least 95%. Another antibody, 10-77 IgM had no effect on the binding of EGF to A431 cells. Both of antibodies immunopreclpitated EGFR from Triton X-100 extracts of A431 membranes.We tested 12-93 IgG which. inhibits the binding of EGF to its receptor in vitro and in vivo for intrinsic growth promoting activity for squamous cell carcinoma cells and salivary gland adenocarcinoma cells which exhibit opposite growth response to nanomolar concentration of eGF.Furthermore, the expression of EGFR in normal oral mucosa, squamous cell carcinoma, normal salivary gland and salivary gland tumors was determined by immuno-histchemical studies using 12-93.We have found monoclonal antibody which inhibits the binding of EGF inhibited the growth of oral squamous cell carcinoma cells and adenocarcinoma cells derived from salivary gland in serum-free culture. Furthermore it also inhibited the formation of these tumors which transplanted in athymic mice.More research is required into the mechanisms by which receptor antibodies cell killing in vivo and into the Tpossible toxic effects of receptor antibodies on normal cells. However, the results obtained are thus far encouraging and indicate that monoclonal antibodies to receptors for growth factors, hormones and transport proteins may eventuallv prove to be viable therapeutic agents. This approach represents a viable alternative to generating tumor-specific monoclonal antibodies.