2024-08-29T16:37:19+08:002019-12-03|
Contact Information
Research Team
Name Position Office Phone Email
Ziang GUOPhD Student (Lab Representative)E12-3017yc07621@um.edu.mo
Jiaqi WANGPhD Student (Lab Representative)E12-3017yc07602@um.edu.mo
Yeneng DAIUM Macao Post-doctoral FellowE12-3017+853 8822 4232yenengdai@um.edu.mo
Yu LIUPhD Student
Guanyu ZHOUPhD StudentE12-3017
Yingjun PENGPhD StudentE12-3017
Shengyu FUPhD StudentE12-3017
Fengjuan ZHANGPhD StudentE12-3017
Ziyi YANGPhD StudentE12-3017
Yue WANGPhD Student
Shuxin GUOPhD Student
Guanda JIAOPhD StudentE12-3017
Yuheng GUPhD StudentE12-3017
Gen ZHANGPhD Student
Yixuan CHENPhD Student
Guangyu ZHOUPhD Student
Xue LIPhD Student
Weiqi LUPhD Student
Yang LIUPhD StudentE12-3017+853 8822 4232
Ze CHENPhD Student
Jialin LIPhD Student
Zhizhuo WANGPhD Student
Xing FANPhD Student
Education
PhD Department of Biochemistry, The Chinese University of Hong Kong
MSc College of Life Sciences, Jilin University
BSc College of Life Sciences, Jilin University
Position
2021 – Present Associate Professor, Faculty of Health Sciences, University of Macau
2016 – 2021 Assistant Professor, Faculty of Health Sciences, University of Macau
2013 – 2016 Principle Investigator, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
2011 – 2013 Research Associate, Memorial Sloan-Kettering Cancer Center
2008 – 2011 Postdoctoral Fellow, National Cancer Institute, NIH
Research Interests
Our group is interested in the development of antibody-based therapeutics for cancer. The research focuses on engineering of monoclonal antibodies, bispecific antibodies, or chimeric antigen receptors (CARs), the delivery of drugs via the nanoparticles. We are identifying novel human monoclonal antibodies from antibody phage libraries. Monoclonal antibodies are designed to destroy tumor cells by utilizing mechanisms of antibody-dependent cellular cytotoxicity (ADCC) or antibody-drug conjugation (ADC). By using these antibodies as vehicles, bispecific antibodies directed at tumor antigens and human CD3 can engage T cells to lyse tumors. Additionally, all of these antibodies can be reshaped to build CAR to redirect T cells. Meanwhile, based on various antibody and immune cell formats, nanoparticle drug delivery systems are built for the targeted delivery and controlled release of therapeutic agents.

Areas of Expertise:

(1) Antibody-based therapeutics; (2) Immune cell therapy; (3) Antibody display systems; (4) Nanomedicine

Representative Publications
  1. Dai Y, Guo Z, Leng D, Jiao G, Chen K, Fu M, Liu Y, Shen Q, Wang Q*, Zhu L*, Zhao Q*. Metal-coordinated NIR-II nanoadjuvants with nanobody conjugation for potentiating immunotherapy by tumor metabolism reprogramming.  Advanced Science. 2024 Jul 7:e2404886.
  2. Zhou G, Zhang Y, Cao B, Yu D, Gu Y, Fu, S, Liu M, Ouyang D*, Zhao Q*. Enhanced antibody-mediated cellular cytotoxicity of germline-like anti-HER2 antibodies through a point mutation in complementarity-determining regions. Journal of Immunology. 2024 (revision)
  3. Gu Y, Zhao Q*. Clinical Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors. Molecular Diagnosis & Therapy. 2024 Aug 22. doi: 10.1007/s40291-024-00734-w.
  4. Zhou G, Fu S, Zhang Y, Li S, Guo Z, Ouyang D, Ying T, Lu Y*, Zhao Q*. Antibody recognition of human epidermal growth factor receptor-2 (HER2) juxtamembrane domain enhances anti-tumor response of chimeric antigen receptor (CAR)-T cells. Antibodies. 2024, 13(2):45.
  5. Dai Y, Zhu L, Li X, Zhang F, Chen K, Jiao G, Liu Y, Yang Z, Guo Z, Zhang B*, Shen Q*, Zhao Q*. A biomimetic cuproptosis amplifier for targeted NIR-II fluorescence/photoacoustic imaging-guided synergistic NIR-II photothermal immunotherapy. Biomaterials, 2024, 305:122455.
  6. Dai Y, Leng D, Guo Z, Wang J, Gu Y, Peng Y, Zhu L*, Zhao Q*. NIR-II excitation self-assembly nanomedicine for targeted NIR-IIa fluorescence imaging-guided cuproptosis-promoted synergistic therapy against triple-negative breast cancer. Chemical Engineering Journal. 2024, 479:147704.
  7. Huang S, Xing F, Dai Y, Zhang Z, Zhou G, Yang S, Liu YC, Yuan Z, Luo KQ, Ying T, Chu D*, Liu TM*, Deng CX*, Zhao Q*. Navigating chimeric antigen receptor-engineered natural killer cells as drug carriers via three-dimensional mapping of the tumor microenvironment. Journal of Controlled Release, 2023, 362:524-535.
  8. Leng D, Yang Z, Sun H, Song C, Huang C, Ip KU, Chen G, Deng CX*, Zhang XD*, Zhao Q*. Comprehensive analysis of tumor microenvironment reveals prognostic ceRNA network related to immune infiltration in sarcoma. Clinical Cancer Research, 2023, 29(19):3986-4001.
  9. Bai G, Sun C, Guo Z, Wang Y, Zeng X, Su Y, Zhao Q*, Ma B*. Accelerating antibody discovery and design with artificial intelligence: Recent advances and prospects. Seminars in Cancer Biology, 2023, 95:13-24.
  10. Dai Y, Zhang F, Chen K, Sun Z, Wang Z, Xue Y, Li M, Fan Q, Shen Q*, Zhao Q*. An Activatable phototheranostic nanoplatform for tumor specific NIR-II fluorescence imaging and synergistic NIR-II photothermal-chemodynamic therapy. Small, 2023, 19(22):e2206053.
  11. Huang S, Yang J, Shen N, Xu Q, Zhao Q.*Artificial intelligence in lung cancer diagnosis and prognosis: Current application and future perspective. Seminars in Cancer Biology, 2023, 89:30-37.
  12. Cao B, Liu M, Wang L, Zhu K, Cai M, Chen X, Feng Y, Yang S, Fu S, Zhi C, Ye X, Zhang J, Zhang Z, Yang X, Zhao M, Wu Q, Xu L, Yang L, Lian H, Zhao Q*, Zhang Z.*  Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer. Nature Communications 2022, 13, 6203.
  13. Ma G, Tan C, Shan Y, Shao N, Wang F, Dimitrov DS, Wang L*, Zhao Q*. An insulin growth factor-I/II-neutralizing monoclonal antibody in combination with epidermal growth factor receptor inhibitors potently inhibits tumor cell growth. Journal of Cancer. 2022, 13(6):1830.
  14. Liu J. Zhang F, Yu J*, Zhao, Q.* Programmed death-ligand 1 expression on CD22-specific chimeric antigen receptor-modified T cells weakens antitumor potential. MedComm, 2022, 3(2):e140
  15. Zhu L, Li J, Guo Z, Kwok HF, Zhao Q*. Synergistic combination of targeted nano-nuclear-reactors and anti-PD-L1 nanobodies evokes persistent T cell immune activation for cancer immunotherapy. Journal of Nanobiotechnology, 2022, 20(1):521.
  16. Liu M, Huang W, Guo Y, Zhou Y, Zhi C, Chen J, Li J, He J, Lian H, Zhou J, Ye X, Hu Y, Hu H, Liu Z, Huang J, Lin L, Cai M, Wang X, Huang J, Zhang Z*, Zhu K*, Zhao Q*, Cao B.* CAR NK‐92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo. Journal of Leukocye Biology,2 022, 112(4):901-911
  17. Liu J, Yang S, Cao B, Zhou G, Zhang F, Wang Y, Wang R, Zhu L, Meng,Y, Hu C, Liang H, Lin X, Zhu K, Chen G, Luo Q, Di L, Zhao Q.* Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes. Journal of Hematology & Oncology, 2021, 14: 21
  18. Zhu L, Liu J, Zhou G, Liu T, Dai Y, Nie G, Zhao, Q.* Remodeling of tumor microenvironment by tumor-targeting nanozymes enhances immune activation of CAR T cells for combination therapy Small 2021, 17(43): e2102624.
  19. Cao B*, Liu M*, Huang J, Zhou J, Li J, Lian H, Huang W, Guo Y, Yang S, Lin L, Cai M, Zhi C, Wu J, Liang L, Hu Y, Hu H, He J, Liang B*, Zhao Q*, Zhu K.* Development of mesothelin-specific CAR NK-92 cells for the treatment of gastric cancer. International Journal of Biological Sciences, 2021, 17(14):3850-3861.
  20. Zhu L, Liu J, Zhou G, Ng HM, Ang IL, Ma G, Liu Y, Yang S, Zhang F, Miao K, Poon TCW, Zhang X, Yuan Z, Deng CX , Zhao Q.* Targeting immune checkpoint B7-H3 antibody-chlorin e6 bioconjugates for spectroscopic photoacoustic imaging and photodynamic therapy. Chemical Communiations, 2019, 26;55(95):14255-14258.
  21. Wang Y, Shan Y, Gao X, Gong R, Zheng J, Zhang X, Zhao Q *.  Screening and expressing HIV-1 specific antibody fragments in saccharomyces cerevisiae. Molecular Immunology, 2018, 103, 279-285
  22. Wu Y , Chen Z , Zhang P , Zhou L , Jiang T , Chen H , Gong P , Dimitrov DS , Cai L*, Zhao Q.* Recombinant-fully-human-antibody decorated highly-stable far-red AIEdots for in vivo HER-2 receptor-targeted imaging. Chemical Communiations, 2018, 54(53):7314-7317.
  23. Li DZ, Han BN, Wei R, Yao GY, Chen Z, Liu J, Poon TCW, Su W, Zhu Z, Dimitrov DS, Zhao Q.* N-terminal α-amino group modification of antibodies using a site-selective click chemistry method. Mabs, 2018, 10(5):712-719.
  24. Chen Z, Liu J, Chu D, Shan Y, Ma G, Zhang H, Zhang XD, Wang P, Chen Q, Deng C, Chen W, Dimitrov DS, Zhao Q.* A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells. International Journal of Biological Sciences,2018, 14(7):799-806.
  25. Li D, Gong R, Zheng J, Chen X, Dimitrov DS, Zhao Q.* Engineered antibody CH2 domains binding to nucleolin: isolation, characterization and improvement of aggregation. Biochemical and Biophysical Research Communications, 2017, 485 (2), 446-453
  26. Zhao Q, Ahmed M, Guo HF, Cheung IY, Cheung NK.* Alteration of electrostatic surface potential enhances affinity and tumor killing properties of anti-ganglioside GD2 monoclonal antibody hu3F8. Journal of Biological Chemistry, 2015, 290 (21), 13017-13027
  27. Zhao Q, Ahmed M, Tassev DV, Hasan A, Kuo TY, Guo HF, O’Reilly R J, Cheung N K.* Affinity maturation of T-cell receptor-like antibodies for Wilms tumor 1 peptide greatly enhances therapeutic potential. Leukemia, 2015, 29 (11), 2238-2247
  28. Zhao Q. Tran H, Dimitrov DS, Cheung NK.* A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma. International Journal of Cancer, 2015, 137 (9), 2243-2252
  29. Feng Y*, Zhao Q*, Chen W, Wang Y, Crowder K, Dimitrov DS. A new bispecific antibody targeting non-overlapping epitopes on IGF2: design, in vitro characterization and pharmacokinetics in macaques. Experimental and Molecular Pathology, 2014, 97 (3), 359-367
  30. Zhao Q, Feng Y, Zhu Z, Dimitrov DS.* Human monoclonal antibody fragments binding to insulin-like growth factors I and II with picomolar affinity. Molecular Cancer Therapeutics, 2011, 10 (9), 1677-1685
Full Publications List

Full Publications List on Google Scholar

Research Grants
2020 – 2024 National Key R&D Program of China (2019YFA0904400): Directed evolution and function characterization of synthetic immune molecules with high throughput
2020 – 2021 Multi-Year Research Grant – University of Macau (MYRG2019-00069-FHS): Targeting B7-H3 with awakened natural killer cells for therapy of non-small-cell lung cancer
2018 – 2021 The international cooperation project of Guangzhou Government (201807010004), Development of targeting PD-1 enhanced WT1-specific T cell therapies in leukemias
2018 – 2021 The Science and Technology Development Fund of Macau (FDCT/0015/2018/A1), Development of potent TCR-minic CAR T cells with multiplex genome editing
2017 – 2020 The Science and Technology Development Fund of Macau (FDCT/131/2016/A3), Multi-targeting therapy of T-cell receptor-mimic antibodies recognizing tumor-specific class I MHC-peptide epitopes
2016 – 2018 International Cooperation Project of Guangdong Province: Studies of insulin-like growth factors as new targets in cancer therapy
2015 – 2018 Natural Science Fund of Guangdong: Novel anti-IGF bispecific antibodies for therapy of breast cancer
2015 National Science Fund of China (31440041), In vitro directed evolution of germline T-cell receptor mimic antibodies for T cell therapy
2014 – 2015 Novo Nordisk- CAS jointed research fund (NNCAS-2013-9), Novel bispecific antibodies for the treatment of autoimmune diseases

 

Patents
  1. Preparation method of cell for expressing anti-CD22 chimeric antigen receptor and PD-L1 blocking protein, expression vector and application, CN111944850A
  2. High-affinity fully-humanized anti-Her 2 monoclonal antibody, and preparation method and application thereof, CN118126188A
  3. An immune adjuvant loaded with 2-deoxy-D-glucose and coupled anti-PD-L1 nanobody and its preparation method and application, CN118320075A
  4. CD22-targeted high-lethality chimeric antigen receptor T-cell and use thereof in preparation of drugs for treating tumors. CN105968210A
  5. IgG hybrid bispecific antibody against TNFα and IL-17a, PCT/CN2015/099847
  6. High affinity anti-GD2 antibodies. PCT/US2014/029308
  7. Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II, PCT/US2012/033128
  8. An engineering recombinant anti-CEA/CD3/CD28 single-chain tri-specific antibody, PCT/US 2009/0117108
Awards
2024 FHS Best Teacher Award (Eminence in Research), University of Macau
2023 FHS Incentive Scheme for Outstanding Academic Staff, University of Macau
2022 FHS Best Paper Award, University of Macau
2011 Federal Technology Transfer Award, NIH

Others
Conference Presentations

  • 1st Symposium of Chinese NIH Young Scholars, Beijing, China 2016
  • 3rd Macau Symposium on Biomedical Sciences, Macau, 2016
  • 2nd Sino-German Symposium, HSCT and Cellular Therapy for Hematological Malignancies, Heidelberg, German, 2015
  • 9th Biennial meeting of  Chinese Society for  Immunology,  Jinan,  China,2014
  • Protein Engineering Summit (PEGS), Shanghai, China, 2014
  • BIT’s 11th Annual Congress of International Drug Discovery Science & Technology, Haikou, China, 2013
  • Annual Congress of Guangdong Society for Immunology, Guangzhou, China, 2013

Teaching of undergraduate students

  1. Immunology and infectious diseases (HSCI3002).
  2. Stem Cells and Regenerative Medicine (HSCI4002)