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目的研究抗Ⅳ型胶原酶单抗3G11及其F(ab′)2、Fab′片段对小鼠肝癌22(H22)及小鼠Lewis癌肺转移的治疗作用。方法ELISA实验检测3G11及其片段与多种肿瘤细胞及Ⅳ型胶原酶的免疫反应性,明胶酶谱法测定其对HT-1080细胞分泌Ⅳ型胶原酶活性的影响,MTT法测定其对H22细胞的细胞毒作用。用小鼠肝癌22及小鼠Lewis肺癌模型评价单抗3G11及其片段抑制肿瘤生长及抗肿瘤转移活性。结果单抗3G11及其片段对多种肿瘤细胞及Ⅳ型胶原酶均呈阳性反应,单抗3G11抑制肿瘤细胞HT-1080分泌Ⅳ型胶原酶的活性。单抗3G11对H22细胞有微弱的细胞毒作用。单抗3G1130mg/kg对小鼠移植性肝癌的抑制率为51·8%,F(ab′)210mg/kg为49·9%,Fab′20mg/kg为39·3%。F(ab′)2片段10mg/kg对小鼠Lewis癌肺转移的抑制率为76%。结论抗Ⅳ型胶原酶单抗3G11及其片段对小鼠移植性肝癌22生长以及对小鼠Lewis癌肺转移有中度抑制作用,可能用于研制抗体靶向药物。
Objective To investigate the therapeutic effect of anti-type Ⅳ collagenase monoclonal antibody 3G11 and its F (ab ’) 2 and Fab’ fragments on the lung metastasis of mouse hepatocarcinoma 22 (H22) and Lewis lung carcinoma in mice. Methods The immunoreactivity of 3G11 and its fragments with various tumor cells and type Ⅳ collagenase was detected by ELISA. The effect of gelatin zymography on the activity of type Ⅳ collagenase secreted by HT-1080 cells was assayed by ELISA. Cytotoxicity. Anti-tumor growth and anti-tumor metastatic activity of monoclonal antibody 3G11 and its fragments were evaluated using mouse hepatocellular carcinoma 22 and mouse Lewis lung carcinoma models. Results McAb 3G11 and its fragments were positive for a variety of tumor cells and type Ⅳ collagenase. Monoclonal antibody 3G11 inhibited the activity of type Ⅳ collagenase secreted by HT-1080 tumor cells. Monoclonal antibody 3G11 has a weak cytotoxic effect on H22 cells. The inhibitory rate of monoclonal antibody 3G1130mg / kg on mouse transplanted liver cancer was 51.8%, that of F (ab ’) 210mg / kg was 49.9%, and that of Fab’20mg / kg was 39.3%. The inhibitory rate of F (ab ’) 2 fragment at 10 mg / kg on Lewis lung carcinoma in mice was 76%. Conclusion The anti-type IV collagenase monoclonal antibody 3G11 and its fragments can inhibit the growth of mouse transplanted hepatocarcinoma 22 and the lung metastasis of Lewis lung carcinoma in mice, and may be used to develop antibody targeting drugs.