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研究员

姓名 李宗海 性别
专家类别 上海市青年科技杰出贡献奖获得者、上海市领军人才、第七届上海市青年科技英才、教育部“新世纪优秀人才、上海市优秀学科带头人、上海市青年科技启明星
学历 博士 职称 研究员
联系电话 021-64436601 电子邮箱 zonghaili@shsmu.edu.cn
通讯地址 上海市斜土路2200弄25号
个人简介

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研究员,上海交通大学医学院及生物医学工程学院博士生导师,科济生物医药(上海)有限公司董事长、首席执行官兼首席科学官。 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。他长期致力于发展有望治愈肿瘤的新药物或治疗手段。迄今已发表论文近百篇,申报国内外发明专利一百多件。他的研究覆盖肿瘤靶点研究、基因治疗、纳米材料、抗体药物和细胞治疗药物。他早期的研究成就是找到了EGFR靶向多肽GE11,被国内外广泛用于基因和药物递送等研究。他目前的主要研究是发展新型的CAR T免疫细胞治疗手段。为了促进产学研成果转化,他创建了科济生物医药(上海)有限公司,目前已有3个CAR T细胞临床试验申请获得中国国家药监局批准,1个CAR T细胞临床试验申请获得美国食品药品监督管理局和加拿大卫生部批准。他是上海市青年科技杰出贡献奖获得者,曾荣获“第七届上海市青年科技英才(成果转化类)”称号,入选上海市领军人才培养计划、上海市优秀学科带头人培养计划、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“和”上海市青年科技启明星计划”。


研究方向





       李宗海通过扎根于基础研究,带领课题组开展了从靶点、新型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:开展全球首个靶向GPC3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)。其中针对肝细胞癌的GPC3 CAR T细胞产品、针对多发性骨髓的BCMA CAR T细胞产品、针对复发/难治性侵袭性非霍奇金B细胞淋巴瘤(B-NHL)的CD19 CAR T细胞产品均已获得国家药监局CDE的临床试验许可,BCMA CAR T细胞临床试验申请获得美国食品药品监督管理局和加拿大卫生部许可。

同时还开展了新型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、靶向Claudin18.2的人源化单克隆抗体AB011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。





科研论文

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. 2019,111(4):409-418

2)        Xiuqi Wu, Hong Luo, Bizhi Shi,Shengmeng Di,Ruixin Sun,Jingwen Su,Ying Liu, Hua Li,Hua Jiang,and Zonghai Li#. Combined Antitumor Effects of Sorafenib and GPC3-CAR T Cells in Mouse Models of Hepatocellular Carcinoma. Molecular Therapy. doi: 10.1016/j.ymthe.2019.04.020. [Epub ahead of print]

3)        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

4)        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

5)        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

6)        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;

7)        Ying Liu,Shengmeng Di, Bizhi Shi,Honghong Zhang,Yi Wang,Xiuqi Wu,Hong Luo, Huamao Wang, Zonghai Li#, and Hua Jiang#. Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3–Targeted Chimeric Antigen Receptor–Engineered T Cells in Hepatocellular Carcinoma. J Immunol. 2019, 203(1):198-207

8)        Shengmeng Di, Min Zhou, Zeyan Pan, Ruixin Sun, Muhua Chen, hua jiang, Bizhi Shi, Hong Luo, Zonghai Li#. Combined adjuvant of poly I:C improves antitumor effects of CAR-T cells. Front. Oncol. 2019,9:241

9)        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

10)     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

11)     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

12)     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

13)     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

14)     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

15)     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

16)     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.

17)     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

18)     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.

19)     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

20)      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.

21)      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.

22)     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. 

23)     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.

24)     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

25)      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.


科研项目

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)   国家“重大新药创制”科技重大专项,2018ZX09733001-003-001,GPC3-CAR-T细胞治疗制剂的研发,2018/1-2020/12, 137.39万元,在研,任务负责人

5)   上海市领军人才,80万元,在研,主持

6)   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,已结题,主持

7)   上海市生物医药产学研医合作项目,16DZ1910700,靶向GPC3的CAR-T细胞治疗肝细胞癌与肺鳞癌的临床前研究,2016/9-2018/9, 50万元,已结题,课题负责人

8)   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,已结题,主持

9)   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

10) 上海张江国家自主创新示范区专项发展资金重点项目, 201705-XH-CHJ-C1085-031, sPD1-CARgpc3 T细胞的中试研,2017/1-2019/6, 200万元,结题准备,项目负责人

11) 上海市战略性新兴产业发展专项资金项目,嵌合抗原受体T细胞(CAR-T)研发及产业化,2018/1-2021/12, 4385万元,在研,项目负责人


获得专利

1)   李宗海,高慧萍,蒋华,石必枝,顾健人,编码嵌合抗原受体蛋白的核酸及表达嵌合抗原受体蛋白的T淋巴细胞,2017.06.20,中国,ZL201310108532.2

2)   李宗海,高慧萍,蒋华,石必枝,王华茂,李克桑,王红阳,杨胜利,顾健人,编码GPC-3嵌合抗原受体蛋白的核酸及表达GPC-3嵌合抗原受体蛋白的T淋巴细胞,2017.09.29,中国,ZL201310164725.X

3)   李宗海,张鹏飞,石必枝,王华茂,高慧萍,抗上皮细胞粘附分子和T细胞抗原的双特异性抗体,2016.08.03,中国,ZL201310025302.X

4)   李宗海、蒋华、石必枝、王华茂、孔娟、高慧萍,针对表皮生长因子受体隐蔽表位和T细胞抗原的多功能抗体,2015.06.10,中国,ZL201210094008.x

5)   李宗海,王华茂,蒋华,石必枝,顾健人,杨胜利,Specific binding proteins and uses thereof,2015.01.16,日本,特许第5680087号

6)   李宗海,周敏,王海,石必枝,杨胜利,王红阳,顾健人,表皮生长因子受体的外显子缺失变异体,2015.04.29,中国,ZL201010510056.3

7)   李宗海、杨麟、王华茂、王海、蒋华、石必枝,表皮生长因子受体模拟表位肽及其应用,2015.04.01,中国,ZL201310442612.1

8)   Zonghai Li, Hai Wang, Min Zhou, Xiaorong Pan, Jianren Gu, Shengli Yang,Epidermal Growth Factor Receptor Variants and Pharmaceutical Compositions Thereof,2014.4.22,美国,US8703917B2

9)   Zonghai Li, Min Zhou,  Hai Wang, Bizhi Shi, Shengli Yang, Hongyang Wang, Jianren Gu,Human Epidermal growth factor receptor variant lacking an exon,2014.08.05,美国,US 8,796,421 B2

10) Zonghai Li, Huamao Wang, Hua Jiang, Bizhi Shi, Jianren Gu, Shengli Yang,Specific binding proteins and uses thereof,2014.06.18,欧盟,2481754

11) 李宗海,蒋华,王华茂,石必枝,顾健人,用于诊断非小细胞肺癌的血清标志物,2014.04.16,中国,ZL200810207819.X

12) 李宗海,杨麟,王华茂,王海,蒋华,石必枝,表皮生长因子受体模拟表位肽及其应用,2014.07.02,中国,ZL201010023003.9

13) 李宗海,王华茂,蒋华,石必枝,顾健人,杨胜利,Specific binding proteins and uses thereof,2014.12.23,韩国,10-147776

14) Zonghai Li, Huamao Wang, Hua Jiang, Bizhi Shi, Jianren Gu, Shengli Yang,Anti-EFGRv3 monoclonal antibody,2013.08.13,美国,US 8,506,963B2

15) 李宗海,王海,周敏,潘晓蓉,顾健人,杨胜利,表皮生长因子受体变异体,2013.12.04,中国,ZL201010100949.0

16) 储茂泉,李宗海,石必枝,用于检测肿瘤的量子点试剂盒,2013.02.13,中国,ZL201010212388.3


实验室成员
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