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抗体导向治疗是肿瘤综合治疗的重要组成部分.成功的抗体导向治疗取决于两个关键因素;一是抗体及与其偶联物的性能.二是特定靶抗原的选择。理想的抗体应至少满足4个条件:( ⅰ)对肿瘤细胞有高度特异性;(ⅱ)能与细胞毒素牢固结合,而又不影响其与靶抗原的结合;( ⅲ)不引发机体对抗体的免疫反应;( ⅳ)必须有效浓集于肿瘤区.自1975年杂交瘤技术问世以来,人们利用单克隆抗体(单抗)识别抗原的高度特异性,针对肿瘤细胞特异或相关抗原进行了大量抗体导向治疗研究,期望这种“魔弹”能特异杀伤肿瘤细胞,而对正常细胞无害.经过20多年的实践,以传统单抗为载体的抗体导向治疗虽然在动物体内取得了成功,而临床效果并不理想.其主要原因是鼠源性单抗在人体反复应用后会引起人抗鼠抗体反应,使临床疗效减弱或消失;由于肿瘤间质高压,使大分子量的完整抗体难以穿透到肿瘤内部,放射性核素示踪研究表明注入体内的抗体仅有 0.01%~0. 1%到达肿瘤部位;另外,肿瘤细胞抗原的异质性,肿瘤细胞的遗传不稳定性所导致的抗药性,亦给针对肿瘤细胞的抗体导向治疗增添了困难.
Antibody-directed therapy is an important part of comprehensive cancer therapy. Successful antibody-directed therapy depends on two key factors; first, the performance of antibodies and their conjugates. Second, the choice of specific target antigens. Ideal antibodies should meet at least four conditions: (i) have high specificity for tumor cells; (ii) bind tightly to cytotoxins without affecting their binding to target antigens; (iii) do not elicit antibodies against the body The immune response; (iv) must be efficiently concentrated in the tumor area. Since the advent of the hybridoma technology in 1975, people have used monoclonal antibodies (mAbs) to recognise the high specificity of antigens, and for tumor cell specific or related antigens. Antibody-directed therapy studies expect that this “magic bullet” can specifically kill tumor cells but not harm normal cells. After more than 20 years of practice, antibody-directed therapy using traditional monoclonal antibodies as vectors has achieved success in animals, but The clinical effect is not ideal. The main reason is that the mouse-derived monoclonal antibody can cause human anti-mouse antibody response after repeated application in the human body, weakening or disappearing clinical efficacy; due to tumor interstitial hypertension, large-molecular-weight intact antibodies are difficult to penetrate. Inside the tumor, radionuclide tracer studies have shown that only 0.01% to 0.1% of the antibodies injected into the body reach the tumor site; in addition, the heterogeneity of tumor cell antigens, the genetic instability of tumor cells. Resistance of the lead, and also to antibodies directed against tumor cells in the treatment adds complications.