李宗海，男，现任上海市肿瘤研究所癌基因及相关基因国家重点实验室生物治疗组课题组长，上海交通大学医学院及生物医学工程学院博士生导师，兼任科济生物医药（上海）有限公司董事长、CEO&CSO。 1997年毕业于湖南医科大学获医学学士学位，2000年获得中南大学医学硕士学位，2005年获得复旦大学医学博士学位。2005年毕业后至今，长期在上海市肿瘤研究所致力于发展有望治愈肿瘤的新药物或治疗手段。迄今已发表论文七十余篇（其中通讯作者SCI收录论文四十多篇，包括在肿瘤领域知名杂志J Natl Cancer Inst、 Cancer Immunol Res、Cancer Res、Clin Cancer Res、Molecular Therapy等，申报国家发明专利60多件，获得授权发明专利21件（其中3件美国专利， 1件韩国专利），他的多项研究成果被国内外广为应用，部分成果已转让给了医药企业（完成发明专利转化9件）。承担国家新药创制重大专项、传染病重大专项、国家自然科学基金以及纵向合作课题等近二十项。2018年获得上海市领军人才培养计划，2016年入选上海市优秀学科带头人培养计划；2014年获得“第七届上海市青年科技英才（成果转化类）”称号，2013年获得教育部“新世纪优秀人才支持计划”，“上海市卫生系统优秀学科带头人培养计划”，以及上海市卫生系统第四十届“银蛇奖”提名奖，2007年获得“上海市青年科技启明星计划”。

李宗海通过扎根于基础研究，带领课题组开展了从靶点、新治疗技术或药物等的大量研究，并与医院和企业进行紧密合作，从而使更多的科研成果早日推进到临床治疗研究中。研究方向主要包括：

1）抗肿瘤免疫细胞治疗药物研究：开展全球首个肝细胞癌的CAR-T临床试验(临床注册号：NCT02395250）及首个EGFR/EGFRvIII双靶点的脑胶质瘤CAR-T临床试验（NCT02331693）。2017年联合多家医院开展新靶点的临床试验，包括针对Claudin18.2的胰腺癌和胃癌（NCT03159819）、靶向BCMA的多发性骨髓瘤（NCT03380039）。同时还开展了新的CAR-T控制安全开关、双靶点CAR-T细胞、新一代增强型CAR-T细胞等研究，为实体瘤的CAR T细胞治疗提供理论基础和临床研究方案；2) 抗体药物的研发: 研制了靶向GPC3、EPCAM的双特异性抗体、靶向肿瘤特异性表位的抗体CH12等，为肿瘤治疗提供新的更加安全有效的潜在候选药物；3）潜在的肿瘤治疗目标识别和验证：克隆了EGFRvA，de4 EGFR等EGFR常见的异构体和突变体，为肿瘤治疗提供了潜在的治疗靶标。相关研究成果发表在J Natl Cancer Inst、 Cancer Immunol Res、Cancer Res、Clin Cancer Res、Molecular Therapy、Biomaterials等专业学术杂志上。

1.         Hua Jiang, Zhimin Shi, PengWang, Cong Wang, Linlin Yang, Guoxiu Du, Honghong Zhang, Bizhi Shi, Jie Jia, Qixiang Li, Huamao Wang, Zonghai Li#. Claudin18.2-Specific Chimeric Antigen Receptor Engineered T Cells for the Treatment of Gastric Cancer. J Natl Cancer Inst. 2018 Sep 6. doi: 10.1093/jnci/djy134. [Epub ahead of print]

2.         Hua Jiang, Huiping Gao, Juan Kong, Bo Song, Peng Wang, Bizhi Shi, Huamao Wang, Zonghai Li#. Selective Targeting of Glioblastoma with EGFRvIII/EGFR Bi-targeted Chimeric Antigen Receptor T Cell. Cancer Immunol Res. 2018 ; 6(11):1314-1326

3.         Min Yu,Hong Luo,Mingliang Fan,Xiuqi Wu,Bizhi Shi,Shengmeng Di,Ying Liu, Zeyan Pan,Hua Jiang,and Zonghai Li#. Development of GPC3-Specific Chimeric Antigen Receptor-Engineered Natural Killer Cells for the Treatment of Hepatocellular Carcinoma. Molecular Therapy. 2018, 26(2):366-378

4.         Zeyan Pan, Shengmeng Di, Bizhi Shi, Hua Jiang, Zhimin Shi, Ying Liu, Yi Wang, Hong Luo, Min Yu, Xiuqi Wu, Zonghai Li#. Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1–CH3 fusion protein. Cancer Immunol Immunother. 2018,67:1621-1634

5.         Xingliang Guo Hua Jiang, Bizhi Shi, Min Zhou, Honghong Zhang,Zhimin Shi, Guoxiu Du, Hong Luo, Xiuqi Wu, Yi Wang, Ruixin Sun and Zonghai Li#. Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells against Hepatocellular Carcinoma. Frontiers Pharmacology. 2018,  9: 1118

6.         Xiuqi Wu, Bizhi Shi, Jiqin Zhang, Zhimin Shi, Shengmeng Di, Minliang Fan, Huiping Gao, Hai Wang, Jianren Gu, Hua Jiang, Zonghai Li#. A fusion receptor as a safety switch, detection and purification biomarker for adoptive transferred T cells. Molecular Therapy. 2017, 25(10):2270-2279

7.         Jiang Hua, Song Bo, Wang Peng, Shi Bizhi, Li Qixiang, Fan Mingliang, Di Shengmeng, Yang Jie, Zonghai Li#. Efficient growth suppression in pancreatic cancer PDX model by fully human anti-mesothelin CAR-T cells. Protein Cell. 2017，8(12):926-931

8.         Yanyu Bi, Hua Jiang, Peng Wang, Bo Song, Huamao Wang, Xianming Kong and Zonghai Li#. Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager. Oncotarget. 2017, 8(32): 52866-52876

9.         Yu Min, Zonghai Li#. Natural killer cells in hepatocellular carcinoma: current status and perspectives for future immunotherapeutic approaches. Front Med. 2017，11(4):509-521

10.     Jiqin Zhang Fei Song, Xiaojing Zhao, Hua Jiang, Xiuqi Wu, Biao Wang, Min Zhou, Mi Tian, Bizhi Shi, Huamao Wang, Yuanhui Jia, Hai Wang, Xiaorong Pan and Zonghai Li#. EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer. Molecular Cancer. 2017, 16:127

11.     Cheng Chen, Kesang Li, Hua Jiang, Fei Song, Huiping Gao, Xiaorong Pan, Bizhi Shi, Yanyu Bi, Huamao Wang, Hongyang Wang, Zonghai Li#. Development of T cells carrying two complementary chimeric antigen receptors against glypican-3 and asialoglycoprotein receptor 1 for the treatment of hepatocellular carcinoma. Cancer Immunol Immunother. 2017, 66(4):475-489

12.     Chen Chong,Liu Kong,Xu yupeng,Zhang Pengwei, Suo Yan, Lu Yi, Zhang Wenyuan, Su Li, Gu Qing,Wang Huamao, Gu Jianren, Zonghai Li#, Xu Xun#. Anti-angiogenesis through noninvasive to minimally invasive intraocular delivery of the peptide CC12 identified by in vivo-directed evolution. Biomaterials. 2017, 112: 218-233

13.     Fei Song, Min Zhou, Biao Wang, Bizhi Shi, Hua Jiang, Jiqin Zhang and Zonghai Li#. Weak binding to E3 ubiquitin ligase c-Cbl increases EGFRvA protein stability. FEBS Lett. 2016，590(9):1345-53.

14.     BiaoWang, Jiqin Zhang, Fei Song, Mi Tian, Bizhi Shi, Hua Jiang, Wen Xu, HaiWang, Min Zhou, Xiaorong Pan, Jianren Gu, Shengli Yang , Liyan Jiang, Zonghai Li#. EGFR regulates iron homeostasis to promote cancer growth through redistribution of transferrin receptor 1. Cancer Letters. 2016，381：331–340

15.     Liang X, Shi B, Wang K, Fan M, Jiao D, Ao J, Song N, Wang C, Gu J, Zonghai Li#. Development of self-assembling peptide nanovesicle with bilayers for enhanced EGFR-targeted drug and gene delivery. Biomaterials. 2016; 82:194-207.

16.     Wen Xu, Yanyu Bi, Juan Kong, Jiqin Zhang, Biao Wang, Kesang Li, Mi Tian,Xiaorong Pan, Bizhi Shi, Jianren Gu, Hua Jiang, Xianming Kong, Zonghai Li#. Combination of an anti-EGFRvIII antibody CH12 with Rapamycin synergistically inhibits the growth of EGFRvIII+PTEN– glioblastoma in vivo. Oncotarget, 2016, 7（17）:24752-24765

17.      Li K, Pan X, Bi Y, Xu W, Chen C, Gao H, Shi B, Jiang H, Yang S, Jiang L, Li Z#. Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma. Oncotarget. 2016 Jan 19; 7(3):2496-507.

18.      Xu W, Bi Y, Zhang J, Kong J, Jiang H, Tian M, Li K, Wang B, Chen C, Song F, Pan X, Shi B, Kong X, Gu J, Cai X, Li Z#. Synergistic antitumor efficacy against the EGFRvIII+HER2+ breast cancers by combining trastuzumab with anti-EGFRvIII antibody CH12.Oncotarget. 2015, 6(36):38840-53.

19.     Hua Jiang*, Qiongna Dong*, Xiaoying Luo, Bizhi Shi, Huamao Wang, Huiping Gao, Juan Kong, Jiqin Zhang, Zonghai Li#. The Monoclonal Antibody CH12 augments 5-fluorouracil-induced Growth Suppression of Hepatocellular Carcinoma Xenografts Expressing Epidermal Growth Factor Receptor Variant III, Cancer Letter, 2014; 342(1):113-120. 

20.     Ma K, Pan X, Fan P, He Y, Gu J, Wang W, Zhang T, Li Z#, Luo X#. Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells. Mol Cancer. 2014, 13:118.

21.     Pengnan Zhang*, Pengfei Zhang*, Bizhi Shi, Hua Jiang, Haiyan Zhan, Min Zhou, Xiaorong Pan, Huiping Gao, Hong Sun# and Zonghai Li#, Galectin-1 overexpression promotes progression and chemoresistance to cisplatin in epithelial ovarian cancer. Cell Death & Disease, 2014,5:e991

22.     Huiping Gao, Kesang Li, Hong Tu, Xiaorong Pan, Hua Jiang, Bizhi Shi, Juan Kong,Hongyang Wang, Shengli Yang, Jianren Gu, and Zonghai Li#. Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma. Clin Cancer Res. 2014,20(24):6418-28；

23.      Pengfei Zhang, Bizhi Shi, Huiping Gao, Hua Jiang, Juan Kong, Jin Yan, Xiaorong Pan, Kesang Li, Pengwei Zhang, Ming Yao, Shengli Yang, Jianren Gu, Hongyang Wang, and Zonghai Li#. Elimination of Hepatocellular carcinoma xenograft with limited galactin-1 expression by a EpCAM/CD3 bispecific antibody. Cancer Immunol Immunother. 2014 ; 63(2):121-132.

24.     Liang X, Li X, Chang J, Duan Y#, Li Z#. Properties and evaluation of quaternized chitosan/lipid cation polymeric liposomes for cancer-targeted gene delivery. Langmuir, 2013; 29(27):8683-8693.

25.     Zhang P, Zhang P, Zhou M, Jiang H, Zhang H, Shi B, Pan X, Gao H, Sun H, Li Z#. Exon 4 deletion variant of epidermal growth factor receptor enhaces invasiveness and cisplatin resistance in epithelial ovarian cancer. Carcinogenesis, 2013; 34(11):2639-2646.

26.     Xiaoying Luo, Xiaolan Long, Hailong Xie, Min Zhou , Zhibin Xu, Bizhi Shi, Hua Jiang, Zonghai Li#. EGFRvⅢ mediates hepatocellular carcinoma cell invasion via promoting S100 calcium binding protein A11 expression. PLOS ONE, 2013; 8(12):e83332.

27.      Min Zhou, Hai Wang, Keke Zhou, Xiaoying Luo, XiaoRong Pan, Bizhi Shi, Hua Jiang, Jiqin Zhang, Kesang Li, Huamao Wang, Huiping Gao, Shun Lu, Ming Yao, Ying Mao, Hong-Yang Wang, Shengli Yang, Jianren Gu, Chuanyuan Li, and Zonghai Li#. A novel EGFR isoform confers increased invasiveness on cancer cells. Cancer Res. 2013; 73(23):7056-7067.

1.   国家自然科学基金面上项目，81872483，嵌合细胞因子受体chIL4-21R对CAR-T细胞的增效作用及其机制研究，2019/01-2022/12，58万元，在研，主持

2.   国家自然科学基金面上项目，81672724，EGFR调控SCD1蛋白稳定性的机制及其对肿瘤发生发展的作用研究，2017/01-2020/12，68.4万元，在研，主持

3.   十三五艾滋病和病毒性肝炎等重大传染病防治专项子课题，2017ZX10203206-006，CARgpc3 T细胞的肝癌联合免疫治疗研究，2017/01-2020/12，169.83万元，在研，主持

4.   上海市优秀学科带头人，16XD1402600，CAR-GPC3 T细胞在肝细胞癌中的早期临床研究，2016.05 -2019.04，40万元，在研，主持

5.   国家自然科学基金面上项目，81472569，表皮生长因子受体异构体EGFRvA对HNRNPF的调控和机制研究，2015/01-2018/12，80万元，在研，主持

6.   上海市卫生和计划生育委员会"新百人计划"，XBR2013123，靶向EGFR与CD3的双特异抗体的研制及用于胶质瘤的实验治疗研究，2014/01-2016/12, 45万元，已结题，主持

7.   上海市卫生和计划生育委员会重点项目, 2105, CH12抗体与顺铂联合用于EGFRvIII阳性非小细胞肺癌的实验治疗研究, 2014/01-2016/12, 10万元，已结题，主持

8.   十二五艾滋病和病毒性肝炎等重大传染病防治专项子课题，2012ZX10002014-006，肝癌靶向性脂质体药物，2012/01-2015/12，175.44万元，已结题，主持

9.  十二五重大新药创制专项子课题，2012ZX09103301-005，抗肿瘤候选药物表皮生长因子受体变异体单克隆抗体CH12的研究，2012/01-2015/12，145.19万元，已结题，主持

工作人员

蒋华    博士  研究员    硕士生导师 

石必枝  硕士  副研究员   

周敏    博士  助理研究员 

梁晓飞  博士  助理研究员 

孙蕊心  博士  助理研究员 

研究生

吴秀奇  博士生

骆红    博士生

王益    博士生

王鹏    博士生

孙艳莎  博士生

陈慕华  硕士生

苏靖雯  硕士生

董一唯  硕士生