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Malgorzata A. Garstka  
研究领域(方向)

Adaptive immune response in diabetes and cancer 

We study the factors that control MHC class I antigen presentation and thus determine how the immune system responds to pathogens and harmful “self” (cancer and autoimmunity). Our work clarified the mechanism of MHC class I antigen presentation. Specifically, we deciphered MHC class I peptide selection, transport of peptide-MHC class I complex to the cell surface for presentation to CD8+ T cells, and the regulation of the MHC class I antigen presentation by the chaperone proteins tapasin and calreticulin. Second, we applied our findings to develop a robust MHC class I multimer technology for the large-scale detection of antigen-specific T cells. We are now exploring MHC class I antigen presentation in type 1 diabetes. Moreover, we study how hyperglycemia in type 2 diabetes affects MHC class I antigen presentation on professional antigen-presenting cells and pancreatic beta cells to understand immune defects in diabetes and diabetes-associated cancer. Last, we develop methods for early detection of gestational diabetes mellitus risk.

本课题组致力于研究MHC I分子抗原呈递过程的调控因素和免疫系统对病原体和有害的“自身刺激”(如癌症和自身免疫)的反应机制,我们的研究发现阐释了MHC I分子的抗原呈递机制,尤其是对MHC I分子的抗原肽选择、抗原肽-MHC I复合体转运至细胞表面并呈递给CD8 + T细胞的过程以及伴侣蛋白Tapasin和钙网蛋白对MHC I分子抗原呈递过程的调控进行了详细的阐述。其次,我们将以上发现应用于开发MHC I分子多聚体技术,以大规模地检测抗原特异性T细胞。目前我们正在进行的研究有:对2型糖尿病中MHC I分子抗原呈递过程的研究;通过研究高血糖如何影响专职抗原递呈细胞和胰腺b细胞中的MHC I分子抗原呈递过程,以了解糖尿病和糖尿病相关性肿瘤中的免疫缺陷机制;研发妊娠期糖尿病的早期诊断方法。

Our main lines of research are:

我们的研究主线包括以下几个方面:

1. MHC class I antigen presentation and adaptive immune response in type 2 diabetes mellitus (T2DM) and T2DM-associated (endometrial or bladder) cancer

Substantial epidemiological evidence supports an association between type 2 diabetes mellitus (T2DM) and increased risk of cancer occurrence and cancer-related mortality. Furthermore, it suggests defects in the immune response against developing cancer in patients with T2DM. We aim to understand the dysfunction in MHC class I antigen presentation and underlying CD8+ T cell response in T2DM and T2DM patients with cancer. We have been deciphering the defects in adaptive immune response in cancer (Publications 4, 6, 11) and diabetes (Publications 1 and 5) and developing diagnostic methods for diabetes (Publication 8). We are now characterizing how T2DM affects bladder cancer severity. Moreover, we study how T2DM influences the adaptive immune response in T2DM patients with endometrial or bladder cancer at the molecular and cellular levels. We analyze patient-derived information and samples using immunohistochemistry, flow cytometry, qRT-PCR, western blot, multi-omics and various statistical and computational methods. Project in collaboration with Urology, Obstetrics and Gynecology and Endocrinology Departments of Second Affiliated Hospital of Xi’an Jiaotong University.

1.2型糖尿病及与2型糖尿病相关的子宫内膜癌患者体内MHC I分子抗原呈递与免疫反应研究

流行病学证据显示2型糖尿病与癌症风险的增加具有相关性,并且会导致死亡率的上升。另有研究表明,2型糖尿病患者存在针对癌细胞的免疫应答缺陷。本课题旨在研究2型糖尿病及合并癌症的患者体内MHC-I类分子抗原呈递紊乱以及CD8+T细胞的免疫应答缺陷机制。我们已经发现了在癌症(4,6,11)和糖尿病(1,5)中的适应性免疫反应缺陷,并开发了糖尿病的诊断方法(8)。目前我们正着力研究2型糖尿病如何影响膀胱癌的发展程度,以及2型糖尿病将如何影响合并了子宫内膜癌或膀胱癌的患者体内的适应性免疫应答。在此过程中,我们对患者来源的生物样本进行免疫组织化学染色、流式细胞术检测、qRT-PCR、免疫印迹、多组学研究,并采用多种不同的统计学方法及计算机技术对患者来源的信息进行深层研究。与西安交通大学第二附属医院泌尿科、妇产科、内分泌科开展合作研究。

2. MHC class I multimer technology for large-scale detection of antigen-specific T cells in autoimmunity and cancer

We found that MHC class I molecules first consider a large peptide pool, subsequently refined by a temperature-sensitive induced-fit mechanism to retain the canonical peptide repertoire. We used this observation to develop MHC multimers, tagged oligomers of MHC molecules loaded with antigenic peptides, reagents for detection, isolation, and characterization of T cells. Our robust technology allows the generation of many different MHC I multimers in parallel using temperature-mediated peptide exchange on HLA-A*02:01 and H-2Kb MHC class I molecules. We employed our multimer technology to monitor the antiviral immune reconstitution in a multiple myeloma patient after T cell-depleted allogeneic stem cell transplantation. In addition, we analyzed CD8+ T cell responses in virus-infected mice. We are now expanding this technology to HLA-A*24:02 alleles to detect autoimmunity in T1DM and anti-bladder cancer immune response (Publications 12, 13, 18, patent). We develop MHC class I multimers using PCR, western blot, FPLC, and flow cytometry. We study patient immune response using multimers, flow cytometry and various statistical methods. Project in collaboration with Urology and Endocrinology Departments of Second Affiliated Hospital of Xi’an Jiaotong University.

2.研发MHC I多聚体技术以大规模检测抗原特异性T细胞

我们发现MHC I分子会在丰富的抗原肽库中通过温度敏感的诱导拟合机制来筛选保留规范的抗原肽。在这一发现的基础上,我们开发了MHC多聚体,将标记有抗原肽、反应物的MHC分子用以检测、分离和表征T细胞。我们可以通过在HLA-A*02:01和H-2Kb MHC I分子上进行温度介导的抗原肽置换,同时生产大量不同的MHC I多聚体。这种多聚体技术被用来监测多发性骨髓瘤患者在T细胞缺乏的异基因干细胞移植术后体内的抗病毒免疫重建过程,并且可以分析病毒感染小鼠体内的CD8+ T细胞反应。目前,此技术还被扩展到对HLA-A*24:02基因型研究中,用以检测T1DM中的自身免疫和抗肿瘤免疫反应(专利, 论文部分12、13, 18)。在研发MHC I多聚体技术的过程中,我们应用了PCR、免疫印迹、快速蛋白液相色谱及流式细胞术,在研究患者免疫应答的过程中,我们使用了多聚体、流式细胞术和多种统计学方法,并与西安交通大学第二附属医院泌尿科及内分泌科开展合作研究。

3. Early detection of gestational diabetes mellitus risk

Gestational diabetes mellitus (GDM) is when a woman without diabetes develops hyperglycemia during pregnancy. GDM poses a risk to the mother and her baby and may progress to type 2 diabetes mellitus later in life. Still, the current diagnosis of GDM is made at 24-28 weeks, leaving little time for the intervention. We aim to detect GDM risk in the first trimester and provide proper treatment and care to the mother to prevent GDM-associated complications. We are developing GDM prediction methods based on a combination of various parameters, including known risk factors, anthropomorphic and clinical indices, genetics and lifestyle indicators using multi-omics, questionnaires, various statistical methods and machine learning algorithms (Publication 3). Our patent application for early GDM detection is 202110193180. Project in collaboration with Obstetrics and Gynecology and Endocrinology Departments of Second Affiliated Hospital of Xi’an Jiaotong University.

3.妊娠期糖尿病危险因素的早期诊断技术

妊娠期糖尿病(GDM)是指原本无糖尿病的女性在怀孕期间出现高血糖表现,对患者及其子女都存在很大的风险,且患者极易在产后发展为2型糖尿病。目前对GDM的诊断主要在怀孕第24-28周,缺乏早期诊断导致对疾病的干预困难。本项目致力于在怀孕第一阶段对GDM发生的风险性进行检测,从而及时给予孕妇相应的诊疗手段以预防妊娠期糖尿病相关并发症的发生。我们的诊断技术研发是以通过多组学、问卷调查、多种统计学方法和机器学习算法等,对包括已知的的危险因素、模拟及临床参数、基因型及生活方式等多种复合参数为基础,并取得了早期GDM检测的专利(202110193180)在这部分研究中,我们与西安交通大学第二附属医院泌尿科、妇产科、内分泌科开展了深度合作。

4. MHC class I antigen presentation in type 1 diabetes mellitus

In type 1 diabetes mellitus (T1DM), insulin-producing pancreatic cells are destroyed by auto-reactive T cells. MHC class I molecules have only recently been recognized as a risk factor for T1DM, independently of the long-known MHC class II haplotypes. We aim to obtain novel molecular and mechanistic insights about the involvement of the MHC class I antigen presentation pathway in T1DM. These aspects may include the molecular details of peptide binding to MHC class I molecules, the earliest transport steps and quality control of MHC class I molecules, their interaction with chaperones under inflammatory and ER stress conditions present in T1DM, or the interference in MHC class I antigen presentation by viruses. Next, we will test various strategies targeting this pathway to prevent auto-reactive T cell responses ex vivo. The project includes three parts: 1) Cellular characterization of MHC class I in T1DM using PCR, western blot, flow cytometry, confocal microscopy and HPLC; 2) Bioinformatic characterization of dynamics of MHC class I molecules associated with T1DM using computational methods (molecular dynamics simulations, local frustration analysis); 3) Targeting MHC class I in T1D to block adaptive immune response using T1DM cell model, T1DM-derived material, PCR and qRT-PCR, western blot, flow cytometry and confocal microscopy.

4.阐释MHC I分子可能诱发1型糖尿病的机制

在1型糖尿病(T1DM)中,胰腺细胞被自身免疫型T细胞破坏,无法生产胰岛素以维持人体正常的血糖水平。近年来,MHC I分子被认为是T1DM的一种独立的危险因素,其作用与作为T1DM危险因素得到学术界广泛认可的MHC II类分子无关。本课题组致力于对参与T1DM中MHC I抗原呈递途径的新型分子及其机制进行研究,其中包括与MHC I分子结合的抗原肽分子水平的特性、MHC I分子的起始运输步骤及其质量调控,及上述过程在T1DM炎性和内质网应激条件下与分子伴侣的相互作用或对病毒对MHC I抗原呈递的干扰作用。在上述研究的基础上,我们还将进一步研究针对该抗原呈递途径的各种干预措施,以预防体外自身免疫型T细胞的活化,具体分为以下三个部分:1)应用PCR、免疫印迹、流式细胞术、共聚焦显微镜和HPLC对1型糖尿病中的MHC I分子进行细胞水平的验证;2)应用计算机技术(分子动力学刺激、局部挫折性能分析)来从生物信息学的角度研究与T1DM相关的MHC I分子动力学特点;3)在T1DM细胞模型及T1DM患者来源的生物学样本中,通过PCR、qRT-PCR、免疫印迹、流式细胞术和共聚焦显微镜等方法来研究以MHC I分子为靶点,从而阻碍1型糖尿病中的异常免疫活化。

个人及工作简历

2016/09 – present: The Second Affiliated Hospital, Xi’an Jiaotong University, Professor

西安交通大学第二附属医院教授

2009/05 – 2016/08: The Netherlands Cancer Institute, postdoctoral researcher, with Prof. Jacques Neefjes

荷兰癌症研究中心Jacques Neefjes教授团队,博士后研究员

2008/10 –2009/04 Jacobs University Bremen postdoctoral researcher, with Prof. Sebastian Springer

德国不来梅雅各布大学Sebastian Springer教授团队,博士后研究员

2007/09 –2008/09 Leiden University Medical Center postdoctoral researcher, with Prof. Emmanuel Wiertz

荷兰莱顿大学医学中心Emmanuel Wiertz教授团队,博士后研究员

科研项目

International (国际项目)

2021/12-2022/11 Gebze Technical University International Grant “Systematic characterization of structure, dynamics and function of HLA-B39 subtypes to decipher their association with autoimmune (Type 1) diabetes”. Project co-leader together with Prof. Onur Serçinoğlu.

 

National(国家级项目)

1. 2019/01-2022/12 Natural Science Foundation of China Grant “Molecular basis of the strong linkage of HLA-B*39:06 with auto-immune diabetes mellitus (grant number 81870536)”

主持2019年国家自然科学基金青年项目《⾃自身免疫性糖尿尿病和⼈白细胞抗原B3906⾼高度关联的分⼦子机制研究》(81870536)

2. 2018/01-2020/12 Natural Science Foundation of China Grant “Mechanism of MHC I molecules antigen presentation in autoimmunity of type 1 diabetes”

主持2018年国家自然科学基金青年项目《I型主要组织相容性复合体参与1型糖尿病异常自身抗原呈递的机制研究》(81700691)

 

Local(地方项目)

1. The Second Affiliated Hospital of Xi’an Jiaotong University Free Exploration Project “Phenotypic and Functional Characterization of T cell Immune Response in Type 2 Diabetes Mellitus” (82668330)

1.西安交通大学第二附属医院自由探索项目“2型糖尿病中T细胞免疫应答的表型和功能鉴定”(82668330)

2. 2017/01-2019/12 Xi’an Jiaotong University Interdisciplinary Grant “Nanocapsules in blocking CD8 T cells auto-reactivity towards pancreas"

西安交通大学基本科研业务费前沿与综合交叉类项目课题“通过纳米微胶囊靶标MHC I蛋白阻滞CD8 T细胞对胰腺的自身免疫性攻击”

3. 2017/01-2019/12 The Second Affiliated Hospital of Xi’an Jiaotong University Fellowship “Understanding autoimmunity in type 1 diabetes to develop new approaches in patients’ diagnostics” (87679215)

西安交通大学第二附属医院人才培养专项科研基金“了解自身免疫在一型糖尿病中的作用从而发展出新的诊断方法” (87679215)

4. 2016/09-2022/04 Start-up Budget of The Second Affiliated Hospital of Xi’an Jiaotong University “MHC class I antigen presentation in diabetes” (82668428)

西安交通大学第二附属医院启动基金 “糖尿病中的MHC I抗原呈递研究”(82668428)

学术及科研成果、专利、论文

论文:

PUBLICATIONS (cumulative IF 167.838, cumulative citations 1379):

1. Deneen KM and Garstka MA^. Targeted treatment for type 2 diabetes mellitus and sleep disorders from a clinical and neuroimaging perspective. Accepted by Intelligent Medicine https://doi.org/10.1016/j.imed.2022.05.003

2. Lenart I, Truong LH, Nguyen DD, Rasiukienė O, Tsao E, Armstrong J, Kumar P, McHugh K, BI, Maan BS, Garstka MA, Bowness P, Blake N, Powis SJ, Gould K, Nesbeth D and Antoniou AN^. Intrinsic Folding Properties of the HLA-B27 Heavy Chain Revealed by Single Chain Trimer Versions of Peptide-Loaded Class I Major Histocompatibility Complex Molecules, Frontiers in Immunology, 25 July 2022, 3581, https://doi.org/10.3389/fimmu.2022.902135, IF=8.786

3. Zhang R, Viswambharan H,, Cheng CW^, Garstka MA^, Kain K. Inter-ankle Systolic Blood Pressure Difference Is a Marker of Increased Fasting Blood-Glucose in Asian Pregnant Women. Frontiers in Endocrinology, 2022 May 31;13:842254. IF=6.055 doi: 10.3389/fendo.2022.842254 

4. Wieczorek E, Jablonowski Z, Lesicka M, Jablonska E, Kutwin P, Reszka E, and Garstka MA. Genetic contributions of MHC class I antigen processing and presentation pathway to bladder cancer risk and recurrence. Neoplasma, Jan 25:210805N1113. IF=2.575, cited by 1. doi: 10.4149/neo_2021_210805N1113.

5. Gendaszewska-Darmach E^, Garstka MA^, and Błażewska KM^ Targeting Small GTPases and Their Prenylation in Diabetes Mellitus. J. Med. Chem. 2021, 64(14):9677-9710. IF=7.446, cited by 12 (google scholar). https://doi.org/10.1021/acs.jmedchem.1c00410

6. Wieczorek E, Garstka MA^. Recurrent Bladder Cancer in Aging Societies: Importance of Major Histocompatibility Complex Class I Antigen Presentation. Int J Cancer. 2021 148(8):1808-1820. doi: 10.1002/ijc.33359. IF=7.396, cited by 1. https://onlinelibrary.wiley.com/doi/10.1002/ijc.33359

7. Liu J, Garstka MA, Chai Z, Chen Y, Lipkova V, Cooper ME, Mokoena KK, Wang Y, Zhang L. Marriage contributes to higher obesity risk in China: findings from the China Health and Nutrition Survey. Ann Transl Med. 2021 Apr;9(7):564. doi: 10.21037/atm-20-4550, IF=3.932, cited by 2 DOI: 10.21037/atm-20-4550

8. Wang L, Yu X, Xu X, Ming J, Wang Z, Gao B, Xing Y, Zhou J, Fu J, Liu T, Liu X, Garstka MA, Wang X, Ji Q. The fecal microbiota is already altered in normoglycemic individuals who go on to have type 2 diabetes. Front Cell Infect Microbiol. 18 February 2021, IF=4.300, cited by 14 https://doi.org/10.3389/fcimb.2021.598672

9. Li X, Liu X, Zhang Y, Cheng C, Fan J, Zhou J, Garstka MA, Li Z. Hepatoprotective effect of apolipoprotein A4 against carbon tetrachloride induced acute liver injury through mediating hepatic antioxidant and inflammation response in mice. Biochem Biophys Res Commun. Jan 1;534:659-665, IF=3.575, cited by 9 (google scholar). https://doi.org/10.1016/j.bbrc.2020.11.024

10.   Zhang T, Wu KY, Ma N, Wei LL, Garstka M, Zhou W, Li K. The C5a/C5aR2 axis promotes renal inflammation and tissue damage. JCI Insight. 2020 Apr 9;5(7). pii: 134081. doi: 10.1172/jci.insight.134081. IF=8.315, cited by 17 (google scholar). https://doi.org/10.1172/jci.insight.134081

11.   Li BH, Garstka MA, Li ZF. (2019) Chemokines and their receptors promoting the recruitment of myeloid-derived suppressor cells into the tumor. Mol Immunol. 2019 Dec 10;117:201-215. IF=4.407, cited by 79 (google scholar). DOI: 10.1016/j.molimm.2019.11.014

12.   Luimstra J.J., Franken K.L.M.C., Garstka M.A., Drijfhout J.W., Neefjes J.,Ovaa H. (2019). Production and Thermal Exchange of Conditional Peptide‐MHC I Multimers. Curr Protoc Immunol 126 (1), e85, IF=1.76, cited by 8 (google scholar). https://doi.org/10.1002/cpim.85

13.   Luimstra J.J*, Garstka M.A.*^, Roex M.C.J., Redeker A., Janssen G.M.C, van Veelen P.A., Arens R., Falkenburg J.H.F, Jacques Neefjes^, Huib Ovaa^ (2018). A rapid and flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cell responses. J Exp Med 215(5): 1493-1504. IF=10.892, cited by 33 (google scholar). https://doi.org/10.1084/jem.20180156

14.   Song Y., Wu K., Wu W., Duan Z., Gao YF, Zhang L., Chong T., Garstka M.A., Zhou W., and Li K. (2018) Epithelial C5aR1 signalling enhances uropathogenic E coli adhesion to human renal tubular epithelial cells. Frontiers in Immunology 9, 949. IF=6.429, cited by 7 (google scholar). https://doi.org/10.3389/fimmu.2018.00949

15.   Bai F., Zheng W., Dong Y., Wang J., Garstka, M.A., Li R.,, An J., and Ma H. Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and meta-analysis. Oncotarget 9(10):1266-1278, cited by 102 (google scholar). https://doi.org/10.18632/oncotarget.22260

16.   Zhang T., Garstka M., and Li K. (2017). The Controversial C5a Receptor C5aR2: Its Role in Health and Disease. J. Immunol. Res., Article ID 8193932, 16 pages, IF 3.31, cited by 49 (google scholar). https://doi.org/10.1155/2017/8193932

17.   Jongsma M.L.M.,*, Berlin I.,* Wijdeven R.H.M., Janssen L., Janssen G.M.C., Garstka M.A., Janssen H., Mensink M., van Veelen P.A, Spaapen R.M., and Neefjes  J. (2016) ER-associated pathway draws the endosomal system’s architecture for controlled cargo transport. Cell, 166:152-66. IF-28.71, cited by 178 (google scholar), recommended by Prof. Jonathan Bogan (Yale University) and Prof. Brett Collins (University of Queensland) for Faculty of 1000. https://doi.org/10.1016/j.cell.2016.05.078

18.   Garstka M., Fish A., Celie P.H.N., Joosten R.P., Janssen G.M.C., Berlin I., Hoppes R., Stadnik M., Janssen L., Ovaa H., van Veelen P.A., Perrakis A., and Neefjes J. (2015) The first step of peptide selection in antigen presentation by MHC class I molecules. Proc Natl Acad Sci U S A., 112:1505-10. Article, IF-9.81, cited by 65 (google scholar), recommended by Prof. Tim Elliott (University of Southampton, UK) for Faculty of 1000. https://doi.org/10.1073/pnas.1416543112

19.   Garstka M.A^., Neefjes J. (2013). How to target MHC class II into the MIIC compartment. Mol. Immunol., 55: 162-5. IF-3.0, invited review, cited by 13 (google scholar). DOI: 10.1016/j.molimm.2012.10.022

20.   Garstka M.A., Fritzsche S., Lenart I., Hein Z., Jankevicius G., Boyle L.H., Elliott T., Trowsdale J., Antoniou A.N., Zacharias M., and Springer S. (2011). Tapasin dependence of major histocompatibility complex class I molecules correlates with their conformational flexibility. FASEB J., 25: 3989-98. IF-5.71, cited by 71 (google scholar). https://doi.org/10.1096/fj.11-190249

21.   Horst D., Favaloro V., Vilardi F., van Leeuwen H.C., Garstka M.A., Hislop A.D., Rabu C., Kremmer E., Rickinson A.B., High S., Dobberstein B., Ressing M.E., and Wiertz E.J. (2011). EBV Protein BNLF2a Exploits Host Tail-Anchored Protein Integration Machinery To Inhibit TAP. J Immunol., 186: 3594-605. IF-5.79, cited by 49 (google scholar). https://doi.org/10.4049/jimmunol.1002656

22.   Howe C.,* Garstka M.,* Al-Balushi M., Ghanem E., Antoniou A.N., Fritzsche S., Jankevicius G., Kontouli N., Schneeweiss C., Williams A., Elliott T., and Springer S. (2009). Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC Class I molecules. EMBO J., 28: 3730-3744. IF-8.99, cited by 97 (google scholar), recommended by Prof. Joyce Solheim (University of Nebraska Medical Center, USA) for Faculty1000. https://doi.org/10.1038/emboj.2009.296

23.   Palankar R., Skirtach A.G., Kreft O., Bédard M., Garstka M., Gould K., Möhwald H., Sukhorukov G.B., Winterhalter M., and Springer S. (2009). Controlled intracellular release of peptides from microcapsules to follow antigen on MHC class I molecules. Small, 19: 2168-2176. IF-6.17, cited by 129 (google scholar). This article was featured on the cover of the journal. https://onlinelibrary.wiley.com/doi/10.1002/smll.200900809

24.   Schneeweiss C., Garstka M., Smith J., Hütt M.T., Springer S. (2009). The mechanism of action of tapasin in the peptide exchange on MHC class I molecules determined from kinetics simulation studies. Mol Immunol., 46: 2054-2063. Article, IF-2.90 cited by 23 (google scholar).  DOI: 10.1016/j.molimm.2009.02.032

25.   Horst D., van Leeuwen D., Croft N.P., Garstka M.A., Hislop A.D., Kremmer E., Rickinson A.B., Wiertz E.J., Ressing M.E. (2009). Specific targeting of the EBV lytic phase protein BNLF2a to the transporter associated with antigen processing results in impairment of HLA class I-restricted antigen presentation. J Immunol., 182: 2313-2324. IF-5.65, cited by 119 (google scholar). https://doi.org/10.4049/jimmunol.0803218

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*These authors contributed equally to this work

   ^ Corresponding authors

Patents:

-Methods for producing a MHC multimer, publication number: WO/2019/083370 A1, publication date: 2019.05.02, designated states: European Union, Euroasian, African,https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019083370&_cid=P22-K0RXMY-57457-1.

2020/10/29 US patent, application number 16759099, Publication number US2020/0339655 A1; 2020/11/19 China patent, application number 201880081619.6, issue number 20201111600448350.

专利:

MHC多聚体的生产方法,出版号:WO/2019/083370 A1,出版日期:2019.05.02,指定国家:欧盟,欧亚,非洲,https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019083370&_cid=P22-K0RXMY-57457-1. 美国专利,申请号16759099,出版号US2020/0339655 A1;中国专利20/11/19,申请号201880081619.6,发文序号20201111600448350。

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更新日期:2022-09-28