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氨甲喋呤(MTX)和癌胚抗原(CEA)单克隆抗体(McAb)共价结合,制备成MTX-McAb结合物。反应中MTX/McAb为1∶40时,结合物中的MTX/McAb为1∶14,抗体蛋白无明显变性,结合物保留了相当的抗体特异性和药物细胞毒活性。细胞毒试验表明,MTX-McAb对CEA阳性大肠癌细胞HT-29的细胞毒作用明显大于NIgG-MTX和MTX,且能被CEA McAb竞争性阻断。对CEA阴性细胞,MTX-McAb,NIgG-MTX和MTX三者的细胞毒作用无明显差异。提示MTX-McAb通过CEAMcAb的导向作用,能选择性地杀伤CEA阳性细胞。CEA McAb可作为MTX等化疗药物的载体用于CEA阳性肿瘤的治疗。
Methotrexate (MTX) and a carcinoembryonic antigen (CEA) monoclonal antibody (McAb) were covalently linked to prepare an MTX-McAb conjugate. When the ratio of MTX/McAb was 1:40 in the reaction, the MTX/McAb in the conjugate was 1:14, the antibody protein was not significantly denatured, and the conjugates retained considerable antibody specificity and drug cytotoxic activity. The cytotoxicity assay showed that the cytotoxic effect of MTX-McAb on CEA-positive colorectal cancer cells HT-29 was significantly greater than that of NIgG-MTX and MTX, and could be competitively blocked by CEA McAb. There was no significant difference in cytotoxicity between MTX-McAb, NIgG-MTX, and MTX in CEA-negative cells. It is suggested that MTX-McAb can selectively kill CEA positive cells through the guiding effect of CEAMcAb. CEA McAb can be used as a carrier of chemotherapy drugs such as MTX for the treatment of CEA-positive tumors.