2007年8 月，全世界132种生物技术和应用微生物杂志中排名第一，影响因子22.7的国际学术刊物Nature Biotechnology杂志，发表了我校华西临床医学院丘小庆教授的论文《Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting》。该论文被Nature Biotechnology杂志放在其网页的首页作为“本月度最重要的生物技术研究成果”向全世界展示。

在该论文中，丘小庆跳出传统的抗体改造和设计理念，独创性的提出一种抗体模拟物的构建理论。据此理论将分子量十五万的原始抗体改造成了只有三千分子量的多肽模拟物；该模拟物具有优于原始抗体的靶向性，具有原始抗体无法比拟的实体肿瘤穿透性，与原始抗体相比，该模拟物大大降低了免疫原性。

以上述抗体模拟物和细菌毒素为蓝本，丘小庆构建出了一系列新型抗肿瘤物质。在动物模型中有效地杀灭了恶性淋巴肉瘤、肺癌等危害人类的恶性肿瘤。其效力比现有化疗药物强数十倍至上百倍且无化疗药物的毒副作用，对人类攻克癌症病毒做出了重大贡献。

“这是中国人超越世界水平的原始创新发明”，《自然生物技术》杂志主编Andrew Marshall博士这样认为，“这个发明将会动摇免疫学的基础理念”。论文发表后，来自美国、韩国、俄罗斯等国的科学家纷纷致函丘小庆，希望能和他进行合作研究。

Research abstract
Article abstract

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Nature Biotechnology 25, 921 - 929 (2007)
Published online: 5 August 2007 | doi:10.1038/nbt1320

Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting
Xiao-Qing Qiu1, He Wang3, Bei Cai2, Lan-Lan Wang2 & Shi-Tao Yue1

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AbstractHere we show that fusion of two complementarity-determining regions (CDRs), VHCDR1 and VLCDR3, through a cognate framework region (VHFR2) yields mimetics that retain the antigen recognition of their parent molecules, but have a superior capacity to penetrate tumors. The antigen-recognition abilities of these 3 kDa mimetics surpass those of comparable fragments lacking the framework region. In vivo activities of the mimetics suggests that the structural orientation of their CDRs approximates the conxxxxation of the CDRs in the complex of the parent antibody with antigen. We linked the antibody mimetics to the bacterial toxin colicin Ia to create fusion proteins called "pheromonicins," which enable targeted inhibition of tumor growth. In mice bearing human malignant tumors, pheromonicins directed against tumor-specific surface markers show greater capacity to target and penetrate tumors than their parent antibodies. Rational recombination of selected VH/VL binding sites and their framework regions might provide useful targeting moieties for cytotoxic cancer therapies.

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Key Laboratory of Transplant Immunology, Ministry of Health, State Key Laboratory of Biotherapy, No. 37 Wai Nan Guo-xue-Xiang, Chengdu, P.R. of China 610041.
Department of Lab Medicine, Division of Clinical Immunology, West China Hospital, No. 37 Wai Nan Guo-xue-Xiang, Chengdu, P.R. of China 610041.
Laboratory of Genetics, West China Second University Hospital, West China School of Medicine, Sichuan University, No. 37 Wai Nan Guo-xue-Xiang, Chengdu, P.R. of China 610041.
Correspondence to: Xiao-Qing Qiu1 e-mail: xqqiu@tfol.com