张宏恺

教授，博士生导师。国家“四青”，南开大学百名青年学术带头人，国家重点研发计划项目负责人，国药中生-南开大学联合研发中心首席科学家，上海科技大学免化所客座教授。课题组主要从事肿瘤靶向及肿瘤免疫治疗药物的研发工作，同时开展各种抗癌药物的耐药机制研究。我们的工作有望为患者提供创新的疗法（已有3个药物在临床试验），并从分子、细胞、动物模型及临床水平拓展对于癌症如何对各种药物产生抵抗等问题的认识，指导药物开发和联合用药。课题组为博士和硕士研究生提供了优秀的科研条件和生活支持，博士毕业生均以第一作者发表至少一篇十分以上医学一区论文，目前多就职于大学和科研院所、央企或上市药企、三甲医院或到国外知名大学深造。

2004/9-2009/7，南开大学，生物化学与分子生物学，博士 （导师：曹又佳 博士）；2000/9-2004/7，南开大学，生物科学，学士。

2023/8- 南开大学， 药物化学生物学全国重点实验室和生命科学学院，教授；2016/5-2023/7， 南开大学，药物化学生物学国家重点实验室，特聘研究员；2013/10-2016/4，美国The Scripps Research Institute， 高级科学家； 2009/9-2013/9， 美国The Scripps Research Institute， 博士后 （导师：Richard A. Lerner 博士）。

研究方向：

1.新型肿瘤靶向和肿瘤免疫抗体

2.溶瘤病毒及基因疗法

3.血液肿瘤和实体瘤的CAR-T疗法

课题组代表论文

2025年

1. J Zhao, et al. Single-cell data-driven design of armed oncolytic virus to boost cooperative innate-adaptive immunity against cancer. Mol Ther. 2025;33(2):703-722.

2. Z Zhao, et al. The crystal structure of coronavirus RBD-TMPRSS2 complex provides basis for the discovery of therapeutic antibodies. Nat Commun. 2025;16:6636.

3. N Li, et al. The bispecific antibody targeting CD40 and HER2 potentiates therapeutic efficacy by reprogramming macrophages within the tumor microenvironment. Clin. Transl. Med. 2025.

 

2024年

1. N Li, et al. Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcgammaRIIb binding. Mol Ther. 2024;S1525-0016(24):00584-00587.

2. W Lu, et al. Prophylactic donor-derived CD19 CAR-T cell infusion for preventing relapse in high-risk B-ALL after allogeneic hematopoietic stem cell transplantation. Leukemia. 2024;38(6):1419-1422.

 

2023年

1. S Liu, et al. OX40L-Armed Oncolytic Virus Boosts T-cell Response and Remodels Tumor Microenvironment for Pancreatic Cancer Treatment. Theranostics. 2023;13(12):4016-4029.

2. Y Li, et al. Tumor Cell Nanovaccines Based on Genetically Engineered Antibody-Anchored Membrane. Adv Mater. 2023;35(13):e2208923.

 

2022年

1. Y Liang, et al. Self-assembly of X-shaped antibody to combine the activity of IgG and IgA for enhanced tumor killing. Theranostics. 2022;12(18):7729-7744.

2. X Jin, et al. First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia. J Hematol Oncol. 2022;15(1):88.

3. K Ye, et al. An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ. Mol Ther. 2022;30(12):3658-3676.

4. R Wang, et al. CD40L-armed oncolytic herpes simplex virus suppresses pancreatic ductal adenocarcinoma by facilitating the tumor microenvironment favorable to cytotoxic T cell response in the syngeneic mouse model. J Immunother Cancer. 2022;10(1) :e003809.

 

2021年

1. Y Wang, et al. High-throughput functional screening for next-generation cancer immunotherapy using droplet-based microfluidics. Sci Adv. 2021;7(24) :eabe3839.

2. Y Guo, et al. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes. Nat Commun. 2021;12(1):2623.

3. X Zhou, et al. Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine. Protein Cell. 2021;12(10):818-823.

4. D Fu, et al. Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes. PLoS Biol. 2021;19(5):e3001209.

5. L Zhang, et al. Reshaping the Immune Microenvironment by Oncolytic Herpes Simplex Virus in Murine Pancreatic Ductal Adenocarcinoma. Mol Ther. 2021;29(2):744-761.

6. D Chen, et al. A general Fc engineering platform for the next generation of antibody therapeutics. Theranostics. 2021;11(4):1901-1917.

 

回国前代表作

 

1. H Zhang, et al. Autocrine-Based Selection of Drugs That Target Ion Channels from Combinatorial Venom Peptide Libraries. Angew Chem Int Ed Engl. 2016;55(32):9306-9310.

 

2. H Zhang, et al. Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects. Nat Commun. 2015; 1(6):8918. 1.（发现了GLP-1R的biased agonist P5多肽，为多个GLP-1R biased agonist药物的提供了理论基础）

 

3. H Zhang, Yea K, Xie J, Ruiz D, Wilson I A, Lerner R A. Selecting agonists from single cells infected with combinatorial antibody libraries. Cell Chem Biol. 2013;20(5):734-741.

 

4. H Zhang, Wilson I A, Lerner R A. Selection of antibodies that regulate phenotype from intracellular combinatorial antibody libraries. Proc Natl Acad Sci U S A. 2012;109(39):15728-15733. （实现基于活性的抗体组合库筛选）

 

5. H Zhang, Torkamani A, Jones T M, Ruiz D I, Pons J, Lerner R A. Phenotype-information-phenotype cycle for deconvolution of combinatorial antibody libraries selected against complex systems. Proc Natl Acad Sci U S A. 2011;108(33):13456-13461.

多个国家和天津医药专业协会委员会常委和委员

生物化学2-2            

生物医药与健康