抗体工程组

(一)本组简介

本组由罗文新教授担任组长,现有博士后2名,在读博士生7名、在读硕士生10名、技术员5名、本科生若干。本组的主要研究方向为肿瘤和慢乙肝治疗性抗体药物的研发。近年来在肿瘤新靶标的发现、双特异性抗体、抗体药物偶联物、清道夫抗体、纳米抗体等新型抗体研究和CAR-T细胞治疗等方面进行了较为深入的研究,并且推进基础研究中获得的创新型治疗性抗体向产业转化。基于抗体的多种治疗手段,在肝癌、乳腺癌、脑胶质瘤、慢乙肝感染等肿瘤和病毒感染性疾病治疗方面取得了良好的效果,成功申请多项中国和国际发明专利,优选的项目将逐步由合作企业推向临床。研究本组已完成多个国家、省、市项目,目前承担2个国家基金项目、1个传染病重大专项,发表SCI论文30余篇;申请中国发明专利18项、国际发明专利4项,获得授权14项。其中多项原创性成果已申请中国发明专利和PCT国际专利,已获20项中国发明专利授权和24项境外专利授权。

近年来取得的重要进展:1)完成慢乙肝治疗性抗体的分子改造及临床前分子筛选,目前已处于海外一期临床阶段。工程化改造获得的二代治疗性抗体具有低剂量高效清除HBsAg的优点,延长的抗体半衰期,有望成为临床治疗慢乙肝的候选药物。2)获得具有自主知识产权的Anti-Trop2/PD1双特异抗体分子可以有效治疗三阴性乳腺癌,Anti-PD1/IL12免疫细胞因子展现强效的肿瘤清除能力,正在开展分子改造工作。3)初步建立了抗体偶联药物平台,开发了一种稳定性高、靶向性好的纳米抗体偶联药物,在肿瘤球模型中具有较强的肿瘤组织穿透能力和杀伤效果;在荷瘤小鼠模型中,能迅速定位到肿瘤部位并高效累积,可有效抑制小鼠肿瘤的生长,表现出高效的抗肿瘤活性。4)获得一种对肿瘤有效的靶向EGFR的三代CAR-T细胞,通过联合小分子抑制剂改善了CAR-T的耐药性;通过对CAR-T诱导的免疫抑制分子进行筛选,发现了新的肿瘤免疫调控分子,其特异性抗体能恢复T细胞功能,发挥抗肿瘤作用。5)建立了纳米抗体筛选与抗体工程改造平台,快速获得特异性纳米抗体及条件激活型纳米抗体,为新型抗体药物研发提供工具化抗体。

(二)导师

罗文新,博士,教授  wxluo@xmu.edu.cn

(三)正在开展的项目

1. 肿瘤治疗性双特异抗体的研发;

2. 肿瘤靶向的细胞因子融合蛋白研究;

3. 肿瘤治疗抗体偶联药物的研究;

4. 肿瘤治疗性新靶点的发现;

5. 肿瘤CAR-T细胞治疗研究;

6. 慢乙肝治疗性抗体药物研究;

7. 激动型抗体药物研究。

(四)近5年来发表的部分文章


1.  Wang Y, Mei Y, Ao Z, Chen Y, Jiang Y, Chen X, Qi R, Fu B, Tang J, Fang M, You M, Zhang T, Yuan Q*, Luo W*, Xia N. A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy. Antiviral Res. 2022 Feb 17;105265.

2.  Chen Y, Xiang X, Qi R, Wang Y, Huang Y, You M, Xian Y, Wu Y, Fu R, Kang C, Tang J, Yu H, Zhang T, Yuan Q*, Luo W*, Xia N. Novel monkey mAbs induced by a therapeutic vaccine targeting the hepatitis B surface antigen effectively suppress hepatitis B virus in mice. Antib Ther. 2021 Sep 29; 4(4):197-207.

3.  Xu L, Zheng Q, Zhu R, Yin Z, Yu H, Lin Y, Wu Y, He M, Huang Y, Jiang Y, Sun H, Zha Z, Yang H, Huang Q, Zhang D, Chen Z, Ye X, Han J, Yang L, Liu C, Que Y, Fang M, Gu Y, Zhang J, Luo W, Zhou Z.H*, Li S*, Cheng T*, Xia N*. Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating. Cell Host Microbe. 2021 Feb 3;S1931-3128(21)00001-9.

4.  Liu X, Liu C, Liu G, Luo W*, Xia N. COVID-19: Progress in diagnostics, therapy and vaccination. Theranostics. 2020 Jun 19;10(17): 7821-7835.

5.  Xia L, Zheng Z, Liu J, Chen Y, Ding J, Xia N, Luo W*, Liu W*. EGFR-targeted CAR-T cells are potent and specific in suppressing triple-negative breast cancer both in vitro and in vivo. Clin Transl Immunology 2020 May 3;9(5): e01135..

6.  Zhou B, Xia L, Zhang T, You M, Huang Y, He M, Su R, Tang J, Zhang J, Li S, An Z, Yuan Q*, Luo W*, Xia N. Structure guided maturation of a novel humanized anti-HBV antibody and its preclinical development. Antiviral Res. 2020 Mar 12;180: 104757.

7.      Liu X, Liu C, Zheng Z, Chen S, Pang X, Xiang X, Tang J, Ren E, Chen Y, You M, Wang X, Chen X, Luo W*, Liu G*, Xia N*. Vesicular Antibodies: A Bioactive Multifunctional Combination Platform for Targeted Therapeutic Delivery and Cancer Immunotherapy. Adv Mater. 2019 Mar 7:e1808294.

8.      Shen C, Zhang M, Chen Y, Zhang L, Wang G, Chen J, Chen S, Li Z, Wei F, Chen J, Yang K, Guo S, Wang Y, Zheng Q, Yu H, Luo W, Zhang J, Chen H, Chen Y, Xia N. An IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency. Theranostics. 2019 Jan 1;9(1):210-231

9.      Deng M, Gui X, Kim J, Xie L, Chen W, Li Z, He L, Chen Y, Chen H, Luo W, Lu Z, Xie J, Churchill H, Xu Y, Zhou Z, Wu G, Yu C, John S, Hirayasu K, Nguyen N, Liu X, Huang F, Li L, Deng H, Tang H, Sadek AH, Zhang L, Huang T, Zou Y, Chen B, Zhu H, Arase H, Xia N, Jiang Y, Collins R, You MJ, Homsi J, Unni N, Lewis C, Chen GQ, Fu YX, Liao XC, An Z, Zheng J, Zhang N, Zhang CC. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature. 2018 Oct;562(7728):605-609.

10.    Zhou B, Xu L, Zhu R, Tang J, Wu Y, Su R, Yin Z, Liu D, Jiang Y, Wen C, You M, Dai L, Lin Y, Chen Y, Yang H, An Z, Fan C*, Cheng T*, Luo W*, Xia N. A bispecific broadly neutralizing antibody against enterovirus 71 and coxsackievirus A16 with therapeutic potential. Antiviral Res. 2018 Nov 9. pii: S0166-3542(18)30463-7

11.    Wang X, An Z, Luo W, Xia N, Zhao Q. Molecular and functional analysis of monoclonal antibodies in support of biologics development. Protein Cell. 2018 Jan;9(1):74-85.

12.    Zhang C, Huang X, Chen S, Li Y, Li Y, Wang X, Tang J, Xia L, Lin Z, Luo W, Li T, Li S, Zhang J, Xia N, Zhao Q. Epitope clustering analysis for vaccine-induced human antibodies in relationship to a panel of murine monoclonal antibodies against HPV16 viral capsid. Vaccine. 2018 Oct 29;36(45):6761-6771

13.    You M, Yang Y, Zhong C, Chen F, Wang X, Jia T, Chen Y, Zhou B, Mi Q, Zhao Q, An Z, Luo W*, Xia N. Efficient mAb production in CHO cells with optimized signal peptide, codon, and UTR. Appl Microbiol Biotechnol. 2018 May 8. doi: 10.1007/s00253-018-8986-5.

14.    Yang Y, You M, Chen F, Jia T, Chen Y, Zhou B, Mi Q, An Z, Luo W*, Xia N*. Efficient Development of a Stable Cell Pool for Antibody Production Using a Single Plasmid. J Biochem. 2018,163(5):391-398

15.    Kang C, Xia L, Chen Y, Zhang T, Wang Y, Zhou B, You M, Yuan Q, Tzeng CM, An Z, Luo W*, Xia N. A novel therapeutic anti-HBV antibody with increased binding to human FcRn improves in vivo PK in mice and monkeys. Protein Cell. 2018, 9(1):130-134.

16.    Wang X, An Z, Luo W, Xia N, Zhao Q*. Molecular and functional analysis of monoclonal antibodies in support of biologics development. Protein Cell. 2018 Jan;9(1):74-85.

17.    Xia L, Su R, An Z, Fu TM, Luo W*.  Human Cytomegalovirus vaccine development: Immune responses to look into vaccine strategy. Human Vaccines & Immunotherapeutics..2018,14(2):292-303.

18.    Xia L, Tang A, Meng W, Freed DC, He L, Wang D, Li F, Li L, Xiong W, Gui X, Schultz RD, Chen H, He X, Swoyer R, Ha S, Liu Y, Morris CD, Zhou Y, Wang IM, Zhao Q, Luo W, Xia N, Espeseth AS, Hazuda DJ, Rupp RE, Barrett AD, Zhang N, Zhu J, Fu TM, An Z. Active evolution of memory B-cells specific to viral gH/gL/pUL128/130/131 pentameric complex in healthy subjects with silent human cytomegalovirus infection. Oncotarget. 2017, 8(43):73654-73669

19.    Shen C, Chen J, Li R, Zhang M, Wang G, Stegalkina S, Zhang L, Chen J, Cao J, Bi X, Anderson SF, Alefantis T, Zhang M, Cai X, Yang K, Zheng Q, Fang M, Yu H, Luo W, Zheng Z, Yuan Q, Zhang J, Wai-Kuo Shih J, Kleanthous H, Chen H, Chen Y, Xia N. A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses. Sci Transl Med. 2017 Oct 18;9(412). pii: eaam5752. doi: 10.1126/scitranslmed.aam5752.

20.    Xia L, Xian Y, Wang D, Chen Y, Huang X, Bi X, Yu H, Fu Z, Liu X, Li S, An Z, Luo W*, Zhao Q, Xia N*. A human monoclonal antibody against HPV16 recognizes an immunodominant and neutralizing epitope partially overlapping with that of H16.V5. Sci Rep. 2016, 6:19042. doi: 10.1038/srep19042.

21.    Zhang TY, Yuan Q, Zhao JH, Zhang YL, Yuan LZ, Lan Y, Lo YC, Sun CP, Wu CR, Zhang JF, Zhang Y, Cao JL, Guo XR, Liu X, Mo XB, Luo WX, Cheng T, Chen YX, Tao MH, Shih JW, Zhao QJ, Zhang J, Chen PJ, Yuan YA, Xia NS. Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen. Gut, 2015.doi:10.1136/gutjnl-2014-308964.

22.    Xia L, Zhang J, Cui C, Bi X, Xiong J, Yu H, An Z, Luo W*, Xia N*. In vitro affinity maturation and characterization of anti-P24 antibody for HIV diagnostic assay. J Biochem. 2015, 158(6):531-538.

23.    Tao Jiang, Daiping Guo, Qian Wang, Xin Wu, Zhao Li, Zhenhua Zheng, Boyuan Yin, Lin Xia, Jixian Tang, Wenxin Luo, Ningshao Xia, Yunbao Jiang. Developing a Genetically Encoded Green Fluorescent Protein Mutant for Sensitive Light-up Fluorescent Sensing and Cellular Imaging of Hg(II). Anal Chim Acta. 2015876: 77-82

24.    You M, Xin L, Yang Y, Zhang X, Chen Y, Yu H, Li S, Zhang J, An Z, Luo W*, Xia N*. Investigation of a special neutralizing epitope of HEV E2s. Protein Cell. 2014 Dec;5(12):950-953.

(五)本组优势

毕业生去向包括赛诺菲、药明康德、养生堂等知名企业,从事抗体药物研发的相关工作,以及在生物、药学、医学相关高校或研究机构任职等。优秀学生有机会获得前往美国德州大学西南医学中心等合作单位的学习机会。

(六)招生要求:

生物学、药学、医学相关专业。

只要你有一颗乐于探索的心,勇于进取的科研精神,积极向上的生活观,对以抗体为手段的肿瘤治疗感兴趣,希望自己的研究成果能造福于人类健康,我们欢迎你的加入。




国家传染病诊断试剂与疫苗工程技术研究中心(厦门大学)  地址:中国福建省厦门市翔安区翔安南路厦门大学翔安校区
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