Title:
PREPARATION METHOD FOR AND USE OF ENHANCED SLIT2 CAR-T CELL AND CAR-NK CELL
Document Type and Number:
WIPO Patent Application WO/2018/053885
Kind Code:
A1
Abstract:
A preparation method for and use of enhanced Slit2 CAR-T cells and CAR-NK cells. The enhanced CAR-T cells and CAR-NK cells are respectively T cells and NK cells containing an enhanced CAR chimeric antigen receptor. The enhanced CAR chimeric antigen receptor includes an extracellular domain capable of binding to an antigen, a transmembrane domain, an intracellular immune costimulatory molecule, an internal ribosome entry site IRES, and HAC-HAS series. The extracellular domain comprises D2 domain of Slit2 protein. The enhanced CAR-T cells and enhanced CAR-NK cells can block programmed cell death-ligand 1 (PDL-1) inhibitory signal, enhance the killing activity of CAR-immune cells, and activate tumor-infiltrating immune cells. The enhanced CAR-immune cells can be used as a cellular drug for the treatment of tumor diseases, so that the modified immune cells can specifically recognize and kill tumors and have an increased high tumor killing activity.
Inventors:
LI HUASHUN (CN)
WANG BAOLEI (CN)
REN BAOYONG (CN)
FANG DONGDONG (CN)
WANG BAOLEI (CN)
REN BAOYONG (CN)
FANG DONGDONG (CN)
Application Number:
PCT/CN2016/101751
Publication Date:
March 29, 2018
Filing Date:
October 11, 2016
Export Citation:
Assignee:
LI HUASHUN (CN)
International Classes:
C07K19/00; A61K48/00; A61P35/00; C12N5/10; C12N15/62
Foreign References:
| CN105837692A | 2016-08-10 | |||
| CN104877028A | 2015-09-02 | |||
| CN105820254A | 2016-08-03 |
Other References:
DATABASE Database PDB 10 October 2012 (2012-10-10), LAZAR-MOLNAR, E. ET AL.: "Chain A, Crystal Structure of the Extracellular Domain of Human Pd-1", Database accession no. 3RRQ_A
MAUTE, R.L. ET AL.: "Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging", PNAS, vol. 112, no. 47, 10 November 2015 (2015-11-10), pages e6506 - e6514, XP002772779
HOHENESTER, E.: "Structural insight into Slit-Robo signalling", BIOCHEM. SOC. TRANS, vol. 36, 31 December 2008 (2008-12-31), pages 251 - 256
DATABASE Nucleotide [O] 6 June 2016 (2016-06-06), "PREDICTED: Homo sapiens slit guidance ligand 2 (SLIT2), transcript variant X4, mRNA", XP055483302, Database accession no. XM_017008845.1
SETH, P. ET AL.: "Magic roundabout, a tumor endothelial marker: Expression and signalling", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 332, 5 May 2005 (2005-05-05), pages 533 - 541, XP027230031
DAI, ZHIANG ET AL.: "Construction anc Expression of 3 FLAG Tags and Determination of Their Affinity Constant", JOURNAL OF ZHEJIANG SCI-TECH UNIVERSITY, vol. 27, no. 2, 31 March 2010 (2010-03-31), pages 313 - 317
MAUTE, R.L. ET AL.: "Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging", PNAS, vol. 112, no. 47, 10 November 2015 (2015-11-10), pages e6506 - e6514, XP002772779
HOHENESTER, E.: "Structural insight into Slit-Robo signalling", BIOCHEM. SOC. TRANS, vol. 36, 31 December 2008 (2008-12-31), pages 251 - 256
DATABASE Nucleotide [O] 6 June 2016 (2016-06-06), "PREDICTED: Homo sapiens slit guidance ligand 2 (SLIT2), transcript variant X4, mRNA", XP055483302, Database accession no. XM_017008845.1
SETH, P. ET AL.: "Magic roundabout, a tumor endothelial marker: Expression and signalling", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 332, 5 May 2005 (2005-05-05), pages 533 - 541, XP027230031
DAI, ZHIANG ET AL.: "Construction anc Expression of 3 FLAG Tags and Determination of Their Affinity Constant", JOURNAL OF ZHEJIANG SCI-TECH UNIVERSITY, vol. 27, no. 2, 31 March 2010 (2010-03-31), pages 313 - 317
Attorney, Agent or Firm:
BRIGHTHEAD INTELLECTUAL PROPERTY AGENCY CO., LTD. (CN)
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