组合单克隆抗体提高人胃癌细胞系及组织反应性的研究

IMPROVEMENTF REACTIVITIES OF THE MONOCLONAL ANTIBODIES COM NATION ON HUMAN GASTRIC CANCER CELL LINES AND TISSUES

采用７种识别不同抗原决定簇的胃癌单克隆抗体３Ｈ１１、３Ｇ９、ＰＤ４、ＰＣ１、ＰＣ６、ＢＢ４．３、３Ｆ４在单一和配对组合应用情况下，观察其与人胃癌细胞系及胃癌组织的反应性。单抗３Ｇ６９、ＢＢ４．３及其组合作用于胃癌细胞系上，经流式细胞仪分析３Ｇ９、ＢＢ４．３与胃细胞结合的膜荧光阳性率分别为７４．２％和５４．９％。平均膜荧光强度分别为５３．６和６５．８．两者合后，在相同抗体浓度下，膜荧光阳性率为９７．４％（Ｐ＜０．０１）；平均膜荧光强度为１２５．５（Ｐ＜００１）．２６例胃癌组织冰冻切片红ＡＢＣ免疫过氧化物酶染色法显示，３Ｇ９、ＢＢ４．３经合后，在相同抗体浓度下与单一单克隆抗体相比，胃癌细胞着染范围增大，染色强度增高。阳性率由单一单克隆抗体的５０．０％，６５．４％，提高到组合后的９６．０％（Ｐ＜０．０１）．单克隆抗３Ｇ９与ＢＢ４．３组合后作用于正常胃癌组织均呈阴性反应，表明单克隆抗体经组合后并未降低单危险抗体的选择性。因此，合理采用组合的单克隆抗体可提高单克隆抗体与人胃癌细胞系及组织的反应性，降低抗原表达的异质性，从而提高单克隆抗体的载体效应。

Seven mouse anti-gastric cancer McAb 3H11,3G9, PD4,PC1, PC6,BB4.3, 3F4,recognizing scparated antigen determinants or epitopes on tumour cells were observed,and compared the reactivity between the single M cAb and M cAb Com bination two by twowith human gastric cancer cell lines and with human gastric cancer tissues. The cell lineM85 were labeled with Single McAb 3G9 or single McAb BB4.3,or Combination of thesetwo M cAbs in the same concentration,and then thesc three gro ups were determined witbflow cytometry (FC M).The results showed that the positiove rate of the previous twogroups were 74. 2% and 54.9% respectively. But the positive rate and MFI of the rcactivityofthe combination group were 97.4%(P<001) and 125.5(P<0.01).The frozen sections in26 cases of gastric cancer tissues were reacted with 3G9,BB4.3 or their combination andthen stained with vectastain ABC peroxidase system. The results revealed that the colnbination of 3G9 and BB4.3. increased significantly with human gastric cancer tissues comparedwith each of the single McAb in the same concentration,i.e. the staining area and stainingintensity of gastric cancer cells were increased,The positive rate of reaction on gastric can-cer tissues was inereased from both 50.0%,64.5% to 96.0%(P<0.01) after combination.The results was negative when the combination of 3GBB9 and BB4.3 reacted with humannormal gastric tiSsues.It indicated that the combination of M cAb did not decrease theselectivity of M cAb.Therefore,the rcactivity could be improved and the heterogeneity ofantigen expression may be overcome by using of the rational combination of McAb withhuman gastric cancer cell Iines and tissues,thus the carrier effects of McAb would be im-proved.