Recombinant polyclonal antibodies for cancer therapy
Recombinant polyclonal antibodies for cancer therapy
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DOI：
10.1002/jcb.20536
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发表时间：
2005-10-01
影响因子：
4
通讯作者：
Williams, BR
中科院分区：
文献类型：
--
作者：
Sharon, J;Liebman, MA;Williams, BR
尽管单克隆抗体越来越多地用于癌症治疗，但由于肿瘤细胞逃逸变体的出现，缓解只是暂时的，不再受抗体的影响。逃逸变体的出现可以通过用多克隆抗体多靶向肿瘤细胞来最小化，多克隆抗体在介导靶破坏的效应子功能方面也将比单克隆抗体更有效。基于肿瘤反应性Fab噬菌体展示文库的构建和筛选，已经开发了用于产生用于癌症治疗的重组多克隆抗体的技术。将选择的Fab质量转化为任何同种型和任何物种的全长多克隆抗体文库（PCAL）。针对人结肠直肠癌细胞系产生的原型PCAL显示，可以获得与正常人细胞相比富集对癌细胞的反应性的多种重组抗体的文库。重组多克隆抗体作为癌症治疗剂的成功将取决于产生、表征和大量生产具有高癌症与正常反应性比率的PCAL的能力，所述PCAL与许多相同类型的癌症交叉反应。
Although monoclonal antibodies are increasingly used for cancer therapy, remissions are only temporary due to emergence of tumor cell escape variants that are no longer affected by the antibody. The emergence of escape variants could be minimized by multi-targeting of tumor cells with polyclonal antibodies, which would also be more efficient than monoclonal antibodies at mediating effector functions for target destruction. A technology for generating recombinant polyclonal antibodies for cancer therapy has been developed based on the construction and selection of tumor-reactive Fab phage display libraries. The selected Fabs are mass-converted to full-length polyclonal antibody libraries (PCALs) of any isotype and any species. Prototypic PCALs generated against human colorectal cancer cell lines showed that libraries of diverse recombinant antibodies, enriched for reactivity to the cancer cells compared to normal human cells, can be obtained. The success of recombinant polyclonal antibodies as cancer therapeutics will depend on the ability to generate, characterize, and mass-produce PCALs with high ratios of cancer-to-normal reactivities that cross-react with many cancers of the same type.