Title:
CONDITION-CONTROLLED SPLICEABLE CHIMERIC ANTIGEN RECEPTOR MOLECULE AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/070527
Kind Code:
A1
Abstract:
A condition-controlled spliceable chimeric antigen receptor molecule and an application thereof. The spliceable chimeric antigen receptor molecule comprises an antigen recognition unit and a signal transduction unit; the antigen recognition unit comprises an antigen recognition structural domain, a transmembrane structural domain, a costimulatory signal domain, an N-terminal splicing domain, and a degrader; and the signal transduction unit comprises a conditional signal response structural domain, a C-terminal splicing domain, and a signaling structural domain. Such a condition-controlled spliceable system can achieve splicing of the two units and signaling under a tumor microenvironment signal. The antigen recognition unit can spontaneously/be induced to degrade, thus reducing retention in normal tissues. A signaling unit can respond to a specific condition signal of a tumor microenvironment, and has the characteristics of low expression in a normal tissue environment and high expression in the tumor microenvironment. The condition-controlled spliceable system can achieve preparation and precise treatment of solid tumor treatment drugs by grafting different functional genes.
Inventors:
XU JIANQING (CN)
ZHANG XIAOYAN (CN)
LIAO QIBIN (CN)
DING XIANGQING (CN)
WANG SHIYU (CN)
ZHANG XIAOYAN (CN)
LIAO QIBIN (CN)
DING XIANGQING (CN)
WANG SHIYU (CN)
Application Number:
PCT/CN2021/127446
Publication Date:
May 04, 2023
Filing Date:
October 29, 2021
Export Citation:
Assignee:
SHANGHAI SINOBAY BIOTECHNOLOGY CO LTD (CN)
International Classes:
C07K19/00; A61K39/00; C12N5/10; C12N15/62
Domestic Patent References:
| WO2020169974A1 | 2020-08-27 | |||
| WO2015092024A2 | 2015-06-25 | |||
| WO2021191447A1 | 2021-09-30 |
Foreign References:
| CN109715808A | 2019-05-03 | |||
| CN109280086A | 2019-01-29 | |||
| CN113348249A | 2021-09-03 | |||
| CN111386263A | 2020-07-07 |
Other References:
KOSTI PARIS, OPZOOMER JAMES W., LARIOS-MARTINEZ KAREN I., HENLEY-SMITH RHONDA, SCUDAMORE CHERYL L., OKESOLA MARY, TAHER MUSTAFA Y.: "Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors", CELL REPORTS MEDICINE, vol. 2, no. 4, 1 April 2021 (2021-04-01), pages 100227, XP093060065, ISSN: 2666-3791, DOI: 10.1016/j.xcrm.2021.100227
QIBIN LIAO;HUAN HE;YUNYU MAO;XIANGQING DING;XIAOYAN ZHANG;JIANQING XU: "Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing", BIOMARKER RESEARCH, BIOMED CENTRAL LTD, LONDON, UK, vol. 8, no. 1, 30 October 2020 (2020-10-30), London, UK , pages 1 - 5, XP021283744, DOI: 10.1186/s40364-020-00238-9
ALEXANDRE JUILLERAT, ALAN MARECHAL, JEAN MARIE FILHOL, YANNICK VALOGNE, JULIEN VALTON, AYMERIC DUCLERT, PHILIPPE DUCHATEAU & LAURE: "An oxygen sensitive self-decision making engineered CAR T-cell", SCIENTIFIC REPORTS, NATURE PUBLISHING GROUP, US, vol. 7, 1 January 2017 (2017-01-01), US , pages 1 - 8, XP002770027, ISSN: 2045-2322, DOI: 10.1038/srep39833
DENG PAN, BAOQIN XUAN, YAMEI SUN, SHAOWU HUANG, MAORONG XIE, YADAN BAI, WENJIA XU, ZHIKANG QIAN: "An intein-mediated modulation of protein stability system and its application to study human cytomegalovirus essential gene function", SCIENTIFIC REPORTS, vol. 6, no. 1, 1 September 2016 (2016-09-01), XP055720896, DOI: 10.1038/srep26167
RICHMAN SARAH A., WANG LIANG-CHUAN, MOON EDMUND K., KHIRE UDAY R., ALBELDA STEVEN M., MILONE MICHAEL C.: "Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo", MOLECULAR THERAPY, ELSEVIER INC., US, vol. 28, no. 7, 1 July 2020 (2020-07-01), US , pages 1600 - 1613, XP093060074, ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2020.06.004
QIBIN LIAO;HUAN HE;YUNYU MAO;XIANGQING DING;XIAOYAN ZHANG;JIANQING XU: "Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing", BIOMARKER RESEARCH, BIOMED CENTRAL LTD, LONDON, UK, vol. 8, no. 1, 30 October 2020 (2020-10-30), London, UK , pages 1 - 5, XP021283744, DOI: 10.1186/s40364-020-00238-9
ALEXANDRE JUILLERAT, ALAN MARECHAL, JEAN MARIE FILHOL, YANNICK VALOGNE, JULIEN VALTON, AYMERIC DUCLERT, PHILIPPE DUCHATEAU & LAURE: "An oxygen sensitive self-decision making engineered CAR T-cell", SCIENTIFIC REPORTS, NATURE PUBLISHING GROUP, US, vol. 7, 1 January 2017 (2017-01-01), US , pages 1 - 8, XP002770027, ISSN: 2045-2322, DOI: 10.1038/srep39833
DENG PAN, BAOQIN XUAN, YAMEI SUN, SHAOWU HUANG, MAORONG XIE, YADAN BAI, WENJIA XU, ZHIKANG QIAN: "An intein-mediated modulation of protein stability system and its application to study human cytomegalovirus essential gene function", SCIENTIFIC REPORTS, vol. 6, no. 1, 1 September 2016 (2016-09-01), XP055720896, DOI: 10.1038/srep26167
RICHMAN SARAH A., WANG LIANG-CHUAN, MOON EDMUND K., KHIRE UDAY R., ALBELDA STEVEN M., MILONE MICHAEL C.: "Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo", MOLECULAR THERAPY, ELSEVIER INC., US, vol. 28, no. 7, 1 July 2020 (2020-07-01), US , pages 1600 - 1613, XP093060074, ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2020.06.004
Attorney, Agent or Firm:
PANAWELL & PARTNERS, LLC (CN)
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