教育背景：

1981年-1985年 南京大学 动物学专业学士
1985年-1988年 南京大学 动物学专业硕士
1995年-1998年 中山大学 分子生物学专业博士
2001年-2003年 美国Rochester大学/George Whipple Cancer Lab 癌症生物学专业 博士后
2003年-2007年 美国MD Anderson Cancer Center 癌症生物学专业博士后

工作经历：

1998年-2001年 中山大学/生物医药研究中心-基因工程药物研究室 主任、副研究员
2008年-2010年 美国MD Anderson Cancer Center/淋巴瘤与骨髓瘤系 研究指导
2011年-2018 美国MD Anderson Cancer Center/淋巴瘤与骨髓瘤系 兼职教授

研究领域：

CAR-T细胞的研究及其转化

1. 什么是CAR-T细胞：

2. CAR-T细胞的作用原理：

CAR-T疗法的基本原理是将T细胞的杀伤效力与抗体的特异性结合起来，从而实现精确地杀死患病细胞。单链可变片段（ScFv）赋予特异性，而细胞内信号域激活T细胞介导的细胞毒性。第一代CAR结构由CD4细胞外结构域与CD3ζ信号结构域结合组成，但这些结构缺乏效力，这推动了包括CD28或4-1BB等共刺激结构域的第二代CAR的发展，这提高了其效应功能和持久性，目前这些CAR-T细胞已被美国FDA批准用于治疗白血病和淋巴瘤等血液类癌症。对这些受体进行微调导致新一代的CAR消除抑制结构域，引入显性负受体或突变共刺激结构域以提高疗效。

3. CAR-T细胞的未来发展方向：

（1）从血液肿瘤的治疗迈向实体肿瘤

（2）从肿瘤治疗进入自身免疫病、抗衰老领域

（3）从自体CAR-T发展到通用现货型异体CAR-T

（4）从基于T细胞的疗法拓展到NK细胞、γδT细胞、TIL、TCRT等等

我们实验室站在全球CAR-T细胞研究领域的最前沿，已有多款全球领先的CAR-T细胞产品获得了美国FDA和欧盟的孤儿药认定、儿科罕见病认定、以及中国CDE的临床试验批件。我们的研究成果正在中国最顶级的临床医院开展临床试验，越来越多的患者也因此获得了康复的机会。我们欢迎有志青年加入我们，共同为造福肿瘤病患做出贡献，给患者们带去新生的希望！

团队成员：

安钢力    双硕士，讲师，实验室管理负责人

汪银燕    博士研究生

张亭亭    博士研究生

邱悦       博士研究生

薛冉       硕士研究生

郑璐       硕士研究生

王晓娜   硕士研究生

马小斐   硕士研究生

顾宇蓝   硕士研究生

黄永康   硕士研究生

霍文慧   硕士研究生

代表性成果：

1. Ma R, You F, Tian S, Zhang T, Tian X, Xiang S, Wu H, Yang N, An G, Yang L. Enhanced efficacy of CD19/CD22 bispecific CAR-T cells with EAAAK linker on B-cell malignancies. Eur J Haematol. 2023 Sep 6. doi: 10.1111/ejh.14090. Epub ahead of print. PMID: 37671595.

2. Wang T, Zhang K, You F, Ma R, Yang N, Tian S, An G, Yang L. Preconditioning of radiotherapy enhances efficacy of B7-H3-CAR-T in treating solid tumor models. Life Sci. 2023 Oct 15;331:122024. doi: 10.1016/j.lfs.2023.122024. Epub 2023 Aug 12. PMID: 37574043.

3. Sheng B, Zhang K, Tian S, Ma R, Li Z, Wu H, Wang T, Jiang L, You F, An G, Meng H, Yang L, Liu X. CD7 protein plays a crucial role in T cell infiltration in tumors. Heliyon. 2023 Jun 15;9(6):e16961. doi: 10.1016/j.heliyon.2023.e16961. PMID: 37416646; PMCID: PMC10320036.

4. Fan S, Wang T, You F, Zhang T, Li Y, Ji C, Han Z, Sheng B, Zhai X, An G, Meng H, Yang L. B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia. Eur J Med Res. 2023 Mar 20;28(1):129. doi: 10.1186/s40001-023-01049-y. PMID: 36941687; PMCID: PMC10026503.

5. Cao X, Dai H, Cui Q, Li Z, Shen W, Pan J, Shen H, Ma Q, Li M, Chen S, Chen J, Zhu X, Meng H, Yang L, Wu D, Tang X. CD7-directed CAR T-cell therapy: a potential immunotherapy strategy for relapsed/refractory acute myeloid leukemia. Exp Hematol Oncol. 2022 Sep 29;11(1):67. doi: 10.1186/s40164-022-00318-6. PMID: 36175988; PMCID: PMC9523980.

6. Li Z, Zhou Z, Tian S, Zhang K, An G, Zhang Y, Ma R, Sheng B, Wang T, Yang H, Yang L. RPRM deletion preserves hematopoietic regeneration by promoting EGFR-dependent DNA repair and hematopoietic stem cell proliferation post ionizing radiation. Cell Biol Int. 2022 Dec;46(12):2158-2172. doi: 10.1002/cbin.11900. Epub 2022 Aug 30. PMID: 36041213; PMCID: PMC9804513.

7. Liu Z, Li X, Li X, Li Z, Chen H, Gong S, Zhang M, Zhang Y, Li Z, Yang L, Liu H. The kidney-expressed transcription factor ZKSCAN3 is dispensable for autophagy transcriptional regulation and AKI progression in mouse. Mutat Res. 2022 Jul-Dec;825:111790. doi: 10.1016/j.mrfmmm.2022.111790. Epub 2022 Jul 9. PMID: 35841832.

8. Zhang M, Chen D, Fu X, Meng H, Nan F, Sun Z, Yu H, Zhang L, Li L, Li X, Wang X, Wang M, You F, Li Z, Chang Y, Zhou Z, Yan J, Li J, Wu X, Wang Y, Wang Y, Xiang S, Chen Y, Pan G, Xu H, Zhang B, Yang L. Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma. Clin Cancer Res. 2022 Jul 1;28(13):2830-2843. doi: 10.1158/1078-0432.CCR-21-4097. PMID: 35435984.

9. Dai HP, Cui W, Cui QY, Zhu WJ, Meng HM, Zhu MQ, Zhu XM, Yang L, Wu DP, Tang XW. Haploidentical CD7 CAR T-cells induced remission in a patient with TP53 mutated relapsed and refractory early T-cell precursor lymphoblastic leukemia/lymphoma. Biomark Res. 2022 Feb 7;10(1):6. doi: 10.1186/s40364-022-00352-w. PMID: 35130959; PMCID: PMC8822664.

10. Zhang T, Wang T, You F, Li Z, Chen D, Zhang K, Tian S, Sheng B, Wu H, Jiang L, Ma R, An G, Meng H, Yang L. Nanobody-based anti-CD22-chimeric antigen receptor T cell immunotherapy exhibits improved remission against B-cell acute lymphoblastic leukemia. Transpl Immunol. 2022 Apr;71:101538. doi: 10.1016/j.trim.2022.101538. Epub 2022 Jan 18. PMID: 35051588.

11. Li Z, Sheng B, Zhang T, Wang T, Chen D, An G, Wang X, Meng H, Yang L. Zkscan3 affects erythroblast development by regulating the transcriptional activity of GATA1 and KLF1 in mice. J Mol Histol. 2022 Apr;53(2):423-436. doi: 10.1007/s10735-021-10052-8. Epub 2021 Dec 23. PMID: 34940950; PMCID: PMC9117376.

12. Chen D, You F, Xiang S, Wang Y, Li Y, Meng H, An G, Zhang T, Li Z, Jiang L, Wu H, Sheng B, Zhang B, Yang L. Chimeric antigen receptor T cells derived from CD7 nanobody exhibit robust antitumor potential against CD7-positive malignancies. Am J Cancer Res. 2021 Nov 15;11(11):5263-5281. PMID: 34873460; PMCID: PMC8640809.

13. Zhai X, You F, Xiang S, Jiang L, Chen D, Li Y, Fan S, Han Z, Zhang T, An G, Zhang B, Chen Y, Meng H, Yang L. MUC1-Tn-targeting chimeric antigen receptor-modified Vγ9Vδ2 T cells with enhanced antigen-specific anti-tumor activity. Am J Cancer Res. 2021 Jan 1;11(1):79-91. PMID: 33520361; PMCID: PMC7840711.

14. You F, Wang Y, Jiang L, Zhu X, Chen D, Yuan L, An G, Meng H, Yang L. A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia. Am J Cancer Res. 2019 Jan 1;9(1):64-78. PMID: 30755812; PMCID: PMC6356925.

15. Zhang P, Zhao S, Wu C, Li J, Li Z, Wen C, Hu S, An G, Meng H, Zhang X, Yang L. Effects of CSF1R-targeted chimeric antigen receptor-modified NK92MI & T cells on tumor-associated macrophages. Immunotherapy. 2018 Aug;10(11):935-949. doi: 10.2217/imt-2018-0012. PMID: 30149762.

16. Tang X, Yang L, Li Z, Nalin AP, Dai H, Xu T, Yin J, You F, Zhu M, Shen W, Chen G, Zhu X, Wu D, Yu J. First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Am J Cancer Res. 2018 Jun 1;8(6):1083-1089. Erratum in: Am J Cancer Res. 2018 Sep 01;8(9):1899. PMID: 30034945; PMCID: PMC6048396.

17. Meng H, Sun X, Song Y, Zou J, An G, Jin Z, Yang L. La/SSB chimeric autoantibody receptor modified NK92MI cells for targeted therapy of autoimmune disease. Clin Immunol. 2018 Jul;192:40-49. doi: 10.1016/j.clim.2018.04.006. Epub 2018 Apr 16. PMID: 29673902.

18. Wang H, Baladandayuthapani V, Wang Z, Lin H, Berkova Z, Davis RE, Yang L, Orlowski RZ. Truncated protein tyrosine phosphatase receptor type O suppresses AKT signaling through IQ motif containing GTPase activating protein 1 and confers sensitivity to bortezomib in multiple myeloma. Oncotarget. 2017 Dec 7;8(69):113858-113873. doi: 10.18632/oncotarget.23017. PMID: 29371952; PMCID: PMC5768369.

19. Chen Y, You F, Jiang L, Li J, Zhu X, Bao Y, Sun X, Tang X, Meng H, An G, Zhang B, Yang L. Gene-modified NK-92MI cells expressing a chimeric CD16-BB-ζ or CD64-BB-ζ receptor exhibit enhanced cancer-killing ability in combination with therapeutic antibody. Oncotarget. 2017 Jun 6;8(23):37128-37139. doi: 10.18632/oncotarget.16201. PMID: 28415754; PMCID: PMC5514896.

20. Yu Y, Li J, Zhu X, Tang X, Bao Y, Sun X, Huang Y, Tian F, Liu X, Yang L. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential. Int J Nanomedicine. 2017 Mar 13;12:1969-1983. doi: 10.2147/IJN.S127575. PMID: 28331319; PMCID: PMC5357075.

21. Zhang XD, Baladandayuthapani V, Lin H, Mulligan G, Li B, Esseltine DW, Qi L, Xu J, Hunziker W, Barlogie B, Usmani SZ, Zhang Q, Crowley J, Hoering A, Shah JJ, Weber DM, Manasanch EE, Thomas SK, Li BZ, Wang HH, Zhang J, Kuiatse I, Tang JL, Wang H, He J, Yang J, Milan E, Cenci S, Ma WC, Wang ZQ, Davis RE, Yang L, Orlowski RZ. Tight Junction Protein 1 Modulates Proteasome Capacity and Proteasome Inhibitor Sensitivity in Multiple Myeloma via EGFR/JAK1/STAT3 Signaling. Cancer Cell. 2016 May 9;29(5):639-652. doi: 10.1016/j.ccell.2016.03.026. Epub 2016 Apr 28. PMID: 27132469; PMCID: PMC4983190.

22. Tang J, Li J, Zhu X, Yu Y, Chen D, Yuan L, Gu Z, Zhang X, Qi L, Gong Z, Jiang P, Yu J, Meng H, An G, Zheng H, Yang L. Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells. Oncotarget. 2016 Jun 7;7(23):34070-83. doi: 10.18632/oncotarget.8710. PMID: 27083001; PMCID: PMC5085138.

23. You F, Jiang L, Zhang B, Lu Q, Zhou Q, Liao X, Wu H, Du K, Zhu Y, Meng H, Gong Z, Zong Y, Huang L, Lu M, Tang J, Li Y, Zhai X, Wang X, Ye S, Chen D, Yuan L, Qi L, Yang L. Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells. Sci China Life Sci. 2016 Apr;59(4):386-97. doi: 10.1007/s11427-016-5024-7. Epub 2016 Mar 7. PMID: 26961900.

24. Chen D, Zou J, Zong Y, Meng H, An G, Yang L. Anti-human CD138 monoclonal antibodies and their bispecific formats: generation and characterization. Immunopharmacol Immunotoxicol. 2016 Jun;38(3):175-83. doi: 10.3109/08923973.2016.1153110. Epub 2016 Mar 8. PMID: 26954291.

25. Zou J, Chen D, Zong Y, Ye S, Tang J, Meng H, An G, Zhang X, Yang L. Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma. Cancer Sci. 2015 May;106(5):512-21. doi: 10.1111/cas.12631. Epub 2015 Mar 13. PMID: 25664501; PMCID: PMC4452151.

获奖情况：

1. 2022年科技部颠覆大赛优胜奖
2. BioCon Awards年度生物技术卓越创始人奖
3. 中国首届药物创新济世奖“年度十大药物创新科学家”
4. 江苏省六大高峰人才团队
5. 江苏省高层次创新创业引进人才