CN107759701B - 嵌合抗原受体、其修饰的NK细胞、编码DNA、mRNA、表达载体、制备方法和应用 - Google Patents
嵌合抗原受体、其修饰的NK细胞、编码DNA、mRNA、表达载体、制备方法和应用 Download PDFInfo
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Abstract
Description
Claims (30)
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Application Number | Priority Date | Filing Date | Title |
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CN201711027016.1A CN107759701B (zh) | 2017-10-27 | 2017-10-27 | 嵌合抗原受体、其修饰的NK细胞、编码DNA、mRNA、表达载体、制备方法和应用 |
PCT/CN2018/094003 WO2019080537A1 (zh) | 2017-10-27 | 2018-07-02 | 包含溶瘤病毒和car-nk细胞的治疗剂及应用、药盒、***和/或癌症的方法 |
PCT/CN2018/094005 WO2019080538A1 (zh) | 2017-10-27 | 2018-07-02 | 嵌合抗原受体、其修饰的NK细胞、编码 DNA、mRNA、表达载体、制备方法和应用 |
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CN112300288B (zh) * | 2019-07-29 | 2022-08-02 | 济南赛尔生物科技股份有限公司 | 一种cik细胞的嵌合抗原受体car及其应用 |
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CN114807042A (zh) * | 2021-01-22 | 2022-07-29 | 南京助天中科科技发展有限公司 | 一种嵌合抗原受体改造的nk细胞及其制备方法与应用 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1423700A (zh) * | 2000-03-24 | 2003-06-11 | 麦克美特股份公司 | 含有针对nkg2d受体复合物的表位的结合位点的多功能多肽 |
WO2016123333A1 (en) * | 2015-01-29 | 2016-08-04 | Regents Of The University Of Minnesota | Chimeric antigen receptors, compositions, and methods |
Non-Patent Citations (2)
Title |
---|
A Chimeric Receptor with NKG2D Specificity Enhances Natural Killer Cell Activation and Killing of Tumor Cells;Yu-Hsiang Chang等;《Cancer Research》;20130109;第73卷(第6期);全文 * |
CAR-NK抗肿瘤研究的现状与发展趋势;殷书磊等;《中国肿瘤生物治疗杂志》;20160219;第23卷(第1期);第1.1.1、3.2节,表1 * |
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