Schaedel Oren, Reiter Yoram
Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Curr Pharm Des. 2006;12(3):363-78. doi: 10.2174/138161206775201983.
The recent developments in the field of recombinant DNA, protein engineering and cancer biology, have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, to regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals; monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and high affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. Upon binding to the Fc Receptor on effector cells, the crystallisable fragment (Fc) region elicits the onslaught of Antigen Dependent Cell-mediated Cytotoxicity (ADCC) and the plasma-native Complement Dependent Cytotoxicity (CDC) response and apoptosis. The progenitor form of the antibody can evolve in to a tailored therapeutic molecule with the help of recombinant DNA technology. Recombinant antibodies may be linked to potent toxins or radio-labeled fragments, conferring a high killing capability. Other recombinant techniques such as ADEPT, conjugate the specificity of antibodies to a prodrug-catalytic subunit thus creating a high local concentration of an activated chemotherapeutic. Antibodies can be used to recruit the adaptive immune response by binding the antibody fragment to a recombinant MHC molecule displaying a highly immunogenic peptide. Apart from their therapeutic capabilities antibodies are powerful detection tools as observed in the operating theater in a procedure known as Radio-immuno-guided Surgery (RIGS).
重组DNA、蛋白质工程和癌症生物学领域的最新进展,使我们深入了解了许多与癌症相关的机制。此外,新技术还催生了一些工具,能够明确区分恶性转化细胞和正常细胞。这种认识为合理设计新时代的药物——单克隆抗体及其片段——铺平了道路。抗体能够以高亲和力特异性地识别抗原,利用这些特性进一步通过特异性识别癌细胞群体的外源抗原来靶向癌细胞。抗体的结构因其功能位点而具有可塑性。当与效应细胞上的Fc受体结合时,可结晶片段(Fc)区域引发抗原依赖性细胞介导的细胞毒性(ADCC)、天然补体依赖性细胞毒性(CDC)反应及细胞凋亡。借助重组DNA技术,抗体的原始形式可演变成一种定制的治疗分子。重组抗体可与强效毒素或放射性标记片段相连,从而具备强大的杀伤能力。其他重组技术,如抗体导向酶前体药物疗法(ADEPT),将抗体的特异性与前体药物催化亚基结合,从而在局部产生高浓度的活化化疗药物。通过将抗体片段与展示高免疫原性肽段的重组MHC分子结合,抗体可用于激发适应性免疫反应。除了具有治疗能力外,抗体还是强大的检测工具,如在手术室中通过放射免疫导向手术(RIGS)所体现的那样。