2021-07-15T17:26:27+08:002019-12-03|
Contact Information
Research Team
Name Position Office Phone Email
Lianwei FENGResearch AssistantN22-3013+853 8822 2953lianweifeng@um.edu.mo
Zihan ZHAOPhD StudentN22-3013+853 8822 2953
Zhizhen CHENPhD StudentN22-3013+853 8822 2953
Guanyu ZHOUPhD StudentN22-3013+853 8822 2953
Shigao HUANGPhD StudentN22-3013+853 8822 2953
Lipeng ZHUPhD StudentN22-3013+853 8822 2953
Yingjun PENGPhD StudentN22-2013+853 8822 2953
Shengyu FUPhD StudentN22-3013+853 8822 2953
Fengjuan ZHANGPhD StudentN22-3013+853 8822 2953
Jiaqi WANGPhD StudentN22-3013+853 8822 2953
Ziang GUOPhD StudentN22-3013+853 8822 2953
Ziyi YANGPhD StudentN22-3013+853 8822 2953
Yue WANGPhD StudentN22-3013+853 8822 2953
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
2016-present 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. Zhu, L., Liu, J., Zhou, G., Liu, T.M., Dai, Y., Nie, G., Zhao, Q., (2021) Remodeling of Tumor Microenvironment by Tumor-targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy. Small DOI: 10.1002/smll.202102624
  2. 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.K., Di, L., Zhao, Q., (2021) Targeting B7-H3 via Chimeric Antigen Receptor T cells and Bispecific Killer Cell Engagers Augments Antitumor Response of Cytotoxic Lymphocytes. J Hematol Oncol14: 21
  3. Zhu, L., Dai, Y., Gao, L., Zhao, Q., (2021) Tumor Microenvironment-Modulated Nanozymes for NIR-II-Triggered Hyperthermia-Enhanced Photo-Nanocatalytic Therapy via Disrupting ROS Homeostasis. Int J Nanomedcicine 16: 4559-4577
  4. Yang, S., Cao, B. H., Zhou, G. Y., Zhu, L. P., Wang, L., Zhang, L., Kwok, H. F., Zhang, Z. F., Zhao, Q. (2020) Targeting B7-H3 Immune Checkpoint with Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity against Non-Small Cell Lung Cancer. Front Pharmacol 11, 1089
  5. Zhu, L. P., Gao, D. Y., Xie, L. S., Dai, Y. L., Zhao, Q. (2020) NIR II-Excited and pH-Responsive Ultrasmall Nanoplatform for Deep Optical Tissue and Drug Delivery Penetration and Effective Cancer Chemophototherapy. Mol Pharm. 17(10):3720-3729.
  6. Zhou, G. Y., Zhao, Q. (2020) Perspectives on Therapeutic Neutralizing Antibodies against the Novel Coronavirus SARS-CoV-2. Int J Biol Sci 16 (10), 1718-1723
  7. Zhao, Q. (2020) Bispecific Antibodies for Autoimmune and Inflammatory Diseases: Clinical Progress to Date. Biodrugs 34 (2), 111-119
  8. Huang, S. G., Zhao, Q. (2020) Nanomedicine-Combined Immunotherapy for Cancer. Curr Med Chem. 27 (34), 5716-5729
  9. Yang, S., Wei, W., Zhao, Q. (2020) B7-H3, a Checkpoint Molecule, as a Target for Cancer Immunotherapy. Int J Biol Sci 16 (11), 1767-1773
  10. Huang, S. G., Yang, J., Fong, S., Zhao, Q. (2019) Artificial Intelligence in Cancer Diagnosis and Prognosis: Opportunities and Challenges. Cancer Lett 471, 61-71
  11. Zhu, L. P., Liu, J., Zhou, G. Y., Ng, H. M., Ang, I. L., Ma, G. F., Liu, Y. B., Yang, S., Zhang, F. J., Miao, K., Poon, T. C. W., Zhang, X. J., Yuan, Z., Deng, C. X., Zhao, Q. (2019) Targeting Immune Checkpoint B7-H3 Antibody-Chlorin E6 Bioconjugates for Spectroscopic Photoacoustic Imaging and Photodynamic Therapy. Chem Commun 55 (95), 14255-14258
  12. Zhu, L. P., Li, P., Gao, D. Y., Liu, J., Liu, Y. B., Sun, C., Xu, M. Z., Chen, X., Sheng, Z. H., Wang, R. B., Yuan, Z., Cai, L., Ma, Y., Zhao, Q. (2019) pH-Sensitive Loaded Retinal/Indocyanine Green Micelles as an “All-in-One” Theranostic Agent for Multi-Modal Imaging in Vivo Guided Cellular Senescence-Photothermal Synergistic Therapy. Chem Commun 55 (44), 6209-6212
  13. Huang, S., Yang, J., Fong, S., Zhao, Q. (2019) Mining Prognosis Index of Brain Metastases Using Artificial Intelligence. Cancers 11 (8), E1140
  14. Hu, D., Zhu, Z., Li, S., Deng, Y., Wu, Y., Zhang, N., Puri, V., Wang, C., Zou, P., Lei, C., Tian, X., Wang, Y., Zhao, Q., Li, W., Prabakaran, P., Feng, Y., Cardosa, J., Qin, C., Zhou, X., Dimitrov, D. S., and Ying, T. (2019) A Broadly Neutralizing Germline-Like Human Monoclonal Antibody against Dengue Virus Envelope Domain III. Plos Pathog 15 (6), e1007836
  15. Liu, J., Zhou, G., Zhang, L., Zhao, Q. (2019) Building Potent Chimeric Antigen Receptor T Cells with CRISPR Genome Editing. Front Immunol 10, 456
  16. Wang, Y., Shan, Y. M., Gao, X. Y., Gong, R., Zheng, J., Zhang, X. H. D., Zhao, Q. (2018) Screening and Expressing HIV-1 Specific Antibody Fragments in Saccharomyces Cerevisiae. Mol Immunol 103, 279-285
  17. Wu, Y. Y., Chen, Z. Z., Zhang, P. F., Zhou, L. H., Jiang, T., Chen, H. J., Gong, P., Dimitrov, D., Cai, L. T., Zhao, Q. (2018) Recombinant-Fully-Human-Antibody Decorated Highly-Stable Far-Red AIEdots for in Vivo HER-2 Receptor-Targeted Imaging. Chem Commun 54 (53), 7314-7317
  18. Li, D.-Z., Han, B. N., Wei, R., Yao, G. Y., Chen, Z. Z., Liu, J., Poon, T., Su, W., Zhu, Z. Y., Dimitrov, D., Zhao, Q. (2018) N-Terminal Alpha-Amino Group Modification of Antibodies Using a Site-Selective Click Chemistry Method. Mabs 10 (5), 712–719
  19. Chen, Z. Z., Liu, J., Chu, D. F., Shan, Y. M., Ma, G. X., Zhang, H. M., Zhang, X. H. D., Wang, P., Chen, Q., Deng, C. X., Chen, W. Z., Dimitrov, D., Zhao, Q. (2018) A Dual-Specific IGF-I/II Human Engineered Antibody Domain Inhibits IGF Signaling in Breast Cancer Cells. Int J Biol Sci 14 (7), 799-806
  20. Xu, T. S., Ying, T. L., Wang, L. L., Zhang, X. H. D., Wang, Y., Kang, L. S., Huang, T., Cheng, L., Wang, L. P., Zhao, Q. (2017) A Native-Like Bispecific Antibody Suppresses the Inflammatory Cytokine Response by Simultaneously Neutralizing Tumor Necrosis Factor-Alpha and Interleukin-17a. Oncotarget 8 (47), 81860-81872
  21. Chu, D. F., Dong, X. Y., Zhao, Q., Gu, J. K., and Wang, Z. J. (2017) Photosensitization Priming of Tumor Microenvironments Improves Delivery of Nanotherapeutics via Neutrophil Infiltration. Adv Mater 29 (27)
  22. Li, D. Z., Gong, R., Zheng, J., Chen, X. H., Dimitrov, D., Zhao, Q. (2017) Engineered Antibody CH2 Domains Binding to Nucleolin: Isolation, Characterization and Improvement of Aggregation. Biochem Bioph Res Co 485 (2), 446-453
  23. Chen, Z. Z., Wang, L. P., Xu, T. S., Wang, Q. F., Kang, L. S., Zhao, Q. (2016) Generation of Bispecific Antibodies by Fc Heterodimerization and Their Application. Curr Pharm Biotechno 17 (15), 1324-1332
  24. Li, D. Z., Liu, J., Zhang, L., Xu, T. S., Chen, J. H., Wang, L. P., Zhao, Q. (2015) N-Terminal Residues of an HIV-1 Gp41 Membrane-Proximal External Region Antigen Influence Broadly Neutralizing 2f5-Like Antibodies. Virologica Sinica 30 (6), 449-456
  25. Zhao, Q., Ahmed, M., Guo, H. F., Cheung, I. Y., and Cheung, N. K. (2015) Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-Ganglioside GD2 Monoclonal Antibody hu3F8. J Biol Chem 290 (21), 13017-13027
  26. Zhao, Q., Ahmed, M., Tassev, D. V., Hasan, A., Kuo, T. Y., Guo, H. F., O’Reilly, R. J., and Cheung, N. K. (2015) Affinity Maturation of T-Cell Receptor-Like Antibodies for Wilms Tumor 1 Peptide Greatly Enhances Therapeutic Potential. Leukemia 29 (11), 2238-2247
  27. Zhao, Q., Tran, H., Dimitrov, D. S., and Cheung, N. K. (2015) A Dual-Specific Anti-IGF-1/IGF-2 Human Monoclonal Antibody Alone and in Combination with Temsirolimus for Therapy of Neuroblastoma. Int J Cancer 137 (9), 2243-2252
  28. Feng, Y.*, Zhao, Q.*, Chen, W., Wang, Y., Crowder, K., and Dimitrov, D. S. (2014) A New Bispecific Antibody Targeting Non-Overlapping Epitopes on IGF2: Design, in Vitro Characterization and Pharmacokinetics in Macaques. Exp Mol Pathol 97 (3), 359-367 (*Co-corresponding authors)
  29. Zhao, Q., Zhu, Z., and Dimitrov, D. S. (2012) Yeast Display of Engineered Antibody Domains. Methods Mol Biol 899, 73-84
  30. Zhao, Q., Feng, Y., Zhu, Z., and Dimitrov, D. S. (2011) Human Monoclonal Antibody Fragments Binding to Insulin-Like Growth Factors I and II with Picomolar Affinity. Mol Cancer Ther 10 (9), 1677-1685
Full Publications List

Full Publications List on Google Scholar

Research Grants
  1. National Key R&D Program of China (2019YFA0904400): Directed evolution and function characterization of synthetic immune molecules with high throughput 2020-2024
  2. 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. 2020-2021
  3. The international cooperation project of Guangzhou Government (201807010004), Development of targeting PD-1 enhanced WT1-specific T cell therapies in leukemias. 2018-2021
  4. The Science and Technology Development Fund of Macau(FDCT/0015/2018/A1), Development of potent TCR-minic CAR T cells with multiplex genome editing, 2018-202
  5. 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 2017-2020
  6. International Cooperation Project of Guangdong Province: Studies of insulin-like growth factors as new targets in cancer therapy, 2016-2018.
  7. Natural Science Fund of Guangdong: Novel anti-IGF bispecific antibodies for therapy of breast cancer, 2015-2018
  8. Novo Nordisk- CAS jointed research fund (NNCAS-2013-9), Novel bispecific antibodies for the treatment of autoimmune diseases. 2014-2015.
  9. National Science Fund of China (31440041), In vitro directed evolution of germline T-cell receptor mimic antibodies for T cell therapy. 2015
Patents
  1. Generation, expression vector and application of lymphocytes expressing anti-CD22 CARs and anti-PD-L1 analogs, Application No: 202010891848.3
  2. Capped Hollow Copper Sulfide Nanoparticles and use thereof. Application No: 201911181237.3
  3. CD22-targeted high-lethality chimeric antigen receptor T-cell and use thereof in preparation of drugs for treating tumors. CN105968210A
  4. IgG hybrid bispecific antibody against TNFα and IL-17a, PCT/CN2015/099847
  5. Expression cassette for antibody expression, expression vector, host cell containing the expression vector, preparation method and applications of the host cell. CN104711253A
  6. High affinity anti-GD2 antibodies. PCT/US2014/029308
  7. Antigen-Binding Proteins Specific for HLA-A2-Restricted Wilms Tumor 1 Peptide, U.S. Patent Application No: 61/944,478
  8. Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II, PCT/US2012/033128
  9. An engineering recombinant anti-CEA/CD3/CD28 single-chain tri-specific antibody, PCT/US 2009/0117108
Awards
Federal Technology Transfer Award, NIH, USA, 2011

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)