Title:
T CELL WITH SILENCED CD59 GENE AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2024/051765
Kind Code:
A1
Abstract:
Provided is a method for promoting T cell proliferation and function by means of intracellular CD59, comprising silencing a CD59 gene in a T cell. Further provided is a nucleic acid molecule for CD59 gene interference. The target sequence in the CD59 gene is represented by SEQ ID NO: 1. Gene editing is carried out by means of shRNA, siRNA or CRISPR-Cas9 technology, and sgRNA specifically targeting the CD59 gene is used for silencing the expression of human CD59 gene. The constructed lentiviral vector realizes heritable silencing of the CD59 gene in the T cell, and the expression level of CD59 in the edited T cell is significantly reduced, resulting in a marked acceleration of cell proliferation and a marked increase in cytokine release, thereby markedly enhancing the function, and providing a new strategy for the treatment of tumors and immune diseases.
Inventors:
LI LUYING (CN)
Application Number:
PCT/CN2023/117395
Publication Date:
March 14, 2024
Filing Date:
September 07, 2023
Export Citation:
Assignee:
SHANGHAI COMGEN BIOPHARMACEUTICAL CO LTD (CN)
International Classes:
C07K16/28; A61K39/395; A61P35/00; C12N7/01
Foreign References:
| TW202221011A | 2022-06-01 | |||
| CN101389658A | 2009-03-18 |
Other References:
XIHE XIE: "Role of CD59Molecules in Antigen-specific Activation of Human T Cells", CHINESE DOCTORAL DISSERTATIONS FULL-TEXT DATABASE), 16 May 2012 (2012-05-16), XP093148303, [retrieved on 20240405]
XI-HE XIE; MEI-HUA GAO; BEI ZHANG; MEI-JUAN WANG; JUAN WANG;: "Post-transcriptional CD59 gene silencing by siRNAs induces enhanced human T lymphocyte response to tumor cell lysate-loaded DCs", CELLULAR IMMUNOLOGY, ACADEMIC PRESS, SAN DIEGO, CA., US, vol. 274, no. 1, 20 February 2012 (2012-02-20), US , pages 1 - 11, XP028412728, ISSN: 0008-8749, DOI: 10.1016/j.cellimm.2012.02.013
SIVASANKAR, B. ET AL.: "A shRNA mediated knockdown approach to understand the role of CD59 in regulation of human CD4+ T cells.", MOLECULAR IMMUNOLOGY, vol. 44, no. 16, 30 September 2007 (2007-09-30), XP022227626, DOI: 10.1016/j.molimm.2007.06.063
SIVASANKAR BAALASUBRAMANIAN, LONGHI M. PAULA, GALLAGHER KATHLEEN M. E., BETTS GARETH J., MORGAN B. PAUL, GODKIN ANDREW J., GALLIMO: "CD59 Blockade Enhances Antigen-Specific CD4+ T Cell Responses in Humans: A New Target for Cancer Immunotherapy?", THE JOURNAL OF IMMUNOLOGY, WILLIAMS & WILKINS CO., US, vol. 182, no. 9, 1 May 2009 (2009-05-01), US , pages 5203 - 5207, XP093147960, ISSN: 0022-1767, DOI: 10.4049/jimmunol.0804243
DATABASE Nucleotide 13 May 2003 (2003-05-13), KALNINE, N. ET AL.: "Homo sapiens CD59 antigen p18-20(antigen identified by monoclonal antibodies 16.3A5,EJ16,EJ30,EL32 and G344) mRNA, complete cds", XP093147964, retrieved from NCBI Database accession no. BT007104.1
WANG LI‑NA, GAO MEI‑HUA, WANG BING, CONG BEI‑BEI, ZHANG SHU‑CHAO: "A role for GPI-CD59 in promoting T-cell signal transduction via LAT", ONCOLOGY LETTERS, SPANDIDOS PUBLICATIONS, GR, 31 January 2018 (2018-01-31), GR , pages 4873 - 4881, XP093147970, ISSN: 1792-1074, DOI: 10.3892/ol.2018.7908
YUAN-YUAN LI, GAO MEI-HUA; CONG BEI-BEI; WANG LI-NA; WANG BING: "The Effect of Activation/down-regulation of CD59 on T Lymphocyte Proliferation", PROGRESS IN MODERN BIOMEDICINE, XIAN DAI SHENG WU YI XUE JIN ZHAN BIAN JI BU, CN, vol. 14, no. 19, 10 July 2014 (2014-07-10), CN , pages 3631 - 3634, XP093148315, ISSN: 1673-6273
YUANYUAN) LI: "Studies on The Role of CD59 in LAT-mediated Signaling in T Lymphocytes", CHINESE MASTER'S THESES FULL-TEXT DATABASE, 28 May 2014 (2014-05-28), XP093148317
YAJUN ZHANG: " Progress in The Regulation of T-Lymphocyte Immunity by The Complement Regulatory Proteins Cd55 And Cd59)", CHINESE JOURNAL OF SPORTS MEDICINE, vol. 29, no. 4, 1 July 2010 (2010-07-01), pages 502 - 505, XP093148322, DOI: 10.16038/j.1000-6710.2010.04.003
XIAOYAN TEN, DU YI GROUP; ZHU KULING; HU XIANGGUO: "Chinese Journal of Cellular and Molecular Immunology", (CHINESE JOURNAL OF CELLULAR AND MOLECULAR IMMUNOLOGY, vol. 29, no. 11, 18 November 2013 (2013-11-18), pages 1215 - 1218, XP093148325, DOI: 10.13423/j.cnki.cjcmi.006921
XI-HE XIE; MEI-HUA GAO; BEI ZHANG; MEI-JUAN WANG; JUAN WANG;: "Post-transcriptional CD59 gene silencing by siRNAs induces enhanced human T lymphocyte response to tumor cell lysate-loaded DCs", CELLULAR IMMUNOLOGY, ACADEMIC PRESS, SAN DIEGO, CA., US, vol. 274, no. 1, 20 February 2012 (2012-02-20), US , pages 1 - 11, XP028412728, ISSN: 0008-8749, DOI: 10.1016/j.cellimm.2012.02.013
SIVASANKAR, B. ET AL.: "A shRNA mediated knockdown approach to understand the role of CD59 in regulation of human CD4+ T cells.", MOLECULAR IMMUNOLOGY, vol. 44, no. 16, 30 September 2007 (2007-09-30), XP022227626, DOI: 10.1016/j.molimm.2007.06.063
SIVASANKAR BAALASUBRAMANIAN, LONGHI M. PAULA, GALLAGHER KATHLEEN M. E., BETTS GARETH J., MORGAN B. PAUL, GODKIN ANDREW J., GALLIMO: "CD59 Blockade Enhances Antigen-Specific CD4+ T Cell Responses in Humans: A New Target for Cancer Immunotherapy?", THE JOURNAL OF IMMUNOLOGY, WILLIAMS & WILKINS CO., US, vol. 182, no. 9, 1 May 2009 (2009-05-01), US , pages 5203 - 5207, XP093147960, ISSN: 0022-1767, DOI: 10.4049/jimmunol.0804243
DATABASE Nucleotide 13 May 2003 (2003-05-13), KALNINE, N. ET AL.: "Homo sapiens CD59 antigen p18-20(antigen identified by monoclonal antibodies 16.3A5,EJ16,EJ30,EL32 and G344) mRNA, complete cds", XP093147964, retrieved from NCBI Database accession no. BT007104.1
WANG LI‑NA, GAO MEI‑HUA, WANG BING, CONG BEI‑BEI, ZHANG SHU‑CHAO: "A role for GPI-CD59 in promoting T-cell signal transduction via LAT", ONCOLOGY LETTERS, SPANDIDOS PUBLICATIONS, GR, 31 January 2018 (2018-01-31), GR , pages 4873 - 4881, XP093147970, ISSN: 1792-1074, DOI: 10.3892/ol.2018.7908
YUAN-YUAN LI, GAO MEI-HUA; CONG BEI-BEI; WANG LI-NA; WANG BING: "The Effect of Activation/down-regulation of CD59 on T Lymphocyte Proliferation", PROGRESS IN MODERN BIOMEDICINE, XIAN DAI SHENG WU YI XUE JIN ZHAN BIAN JI BU, CN, vol. 14, no. 19, 10 July 2014 (2014-07-10), CN , pages 3631 - 3634, XP093148315, ISSN: 1673-6273
YUANYUAN) LI: "Studies on The Role of CD59 in LAT-mediated Signaling in T Lymphocytes", CHINESE MASTER'S THESES FULL-TEXT DATABASE, 28 May 2014 (2014-05-28), XP093148317
YAJUN ZHANG: " Progress in The Regulation of T-Lymphocyte Immunity by The Complement Regulatory Proteins Cd55 And Cd59)", CHINESE JOURNAL OF SPORTS MEDICINE, vol. 29, no. 4, 1 July 2010 (2010-07-01), pages 502 - 505, XP093148322, DOI: 10.16038/j.1000-6710.2010.04.003
XIAOYAN TEN, DU YI GROUP; ZHU KULING; HU XIANGGUO: "Chinese Journal of Cellular and Molecular Immunology", (CHINESE JOURNAL OF CELLULAR AND MOLECULAR IMMUNOLOGY, vol. 29, no. 11, 18 November 2013 (2013-11-18), pages 1215 - 1218, XP093148325, DOI: 10.13423/j.cnki.cjcmi.006921
Attorney, Agent or Firm:
SHANGHAI DIANSHI PARTNERS, P.C. (CN)
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