2007年8 月，全世界132種生物技術和應用微生物雜誌中排名第一，影響因子22.7的國際學術刊物Nature Biotechnology雜誌，發表了我校華西臨床醫學院丘小慶教授的論文《Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting》。該論文被Nature Biotechnology雜誌放在其網頁的首頁作為“本月度最重要的生物技術研究成果”向全世界展示。

在該論文中，丘小慶跳出傳統的抗體改造和設計理念，獨創性的提出一種抗體模擬物的構建理論。據此理論將分子量十五萬的原始抗體改造成了只有三千分子量的多肽模擬物；該模擬物具有優於原始抗體的靶向性，具有原始抗體無法比擬的實體腫瘤穿透性，與原始抗體相比，該模擬物大大降低了免疫原性。

以上述抗體模擬物和細菌毒素為藍本，丘小慶構建出了一系列新型抗腫瘤物質。在動物模型中有效地殺滅了惡性淋巴肉瘤、肺癌等危害人類的惡性腫瘤。其效力比現有化療藥物強數十倍至上百倍且無化療藥物的毒副作用，對人類攻克癌症病毒做出了重大貢獻。

“這是中國人超越世界水平的原始創新發明”，《自然生物技術》雜誌主編Andrew Marshall博士這樣認為，“這個發明將會動搖免疫學的基礎理念”。論文發表後，來自美國、韓國、俄羅斯等國的科學家紛紛致函丘小慶，希望能和他進行合作研究。

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