WO2020181402A1 - 一种抗肿瘤多肽及其应用 - Google Patents

一种抗肿瘤多肽及其应用 Download PDF

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Publication number
WO2020181402A1
WO2020181402A1 PCT/CN2019/074726 CN2019074726W WO2020181402A1 WO 2020181402 A1 WO2020181402 A1 WO 2020181402A1 CN 2019074726 W CN2019074726 W CN 2019074726W WO 2020181402 A1 WO2020181402 A1 WO 2020181402A1
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Prior art keywords
polypeptide
tumor
seq
sequence
tumor activity
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PCT/CN2019/074726
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English (en)
French (fr)
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胡西木
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胡西木
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Priority to PCT/CN2019/074726 priority Critical patent/WO2020181402A1/zh
Publication of WO2020181402A1 publication Critical patent/WO2020181402A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention discloses a polypeptide with anti-tumor activity.
  • the artificially designed polypeptide can simultaneously inhibit the expression of PD-L1 and PD-1 in cells.
  • the invention also discloses key functional fragments of the anti-tumor polypeptide and a derivative form that retains activity.
  • the polypeptide has shown significant anti-tumor activity in mouse tumor-bearing experiments, and can significantly reduce PD-L1 expressed by tumor cells and at the same time reduce PD-1 expressed by immune cells in the tumor microenvironment, thereby promoting tumor killing function
  • the CD8-positive immune cells infiltrate into the tumor tissue, significantly reduce the tumor volume and increase the survival rate of individuals with cancer.
  • the polypeptide of the present invention has a good application prospect in the preparation of anti-tumor drugs.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

一种具有抗肿瘤活性的多肽，该人工设计的多肽能够同时抑制PD-L1和PD-1在细胞内的表达。还公开了该抗肿瘤多肽的关键功能片段以及保留活性的衍生形式。上述多肽在小鼠荷瘤实验中表现了抗肿瘤活性，能够降低肿瘤细胞表达的PD-L1，同时降低肿瘤微环境内免疫细胞表达的PD-1。

Description

无标题
发明名称：本发明公开了一种具有抗肿瘤活性的多肽，该人工设计的多肽能够同时抑制PD-L1和PD-1在细胞内的表达。本发明还公开了该抗肿瘤多肽的关键功能片段以及保留活性的衍生形式。所述的多肽在小鼠荷瘤实验中表现了显著的抗肿瘤活性，能够显著降低肿瘤细胞表达的PD-L1，同时降低肿瘤微环境内免疫细胞表达的PD-1，从而促进具备肿瘤杀伤功能的CD8阳性免疫细胞浸润进入肿瘤组织，显著地缩小肿瘤体积，增加携带癌肿的个体的生存率。本发明所述的多肽作为PD-1和PD-L1的双重抑制剂，在制备抗肿瘤药物方面具有良好的应用前景。
发明概述
技术问题
问题的解决方案
发明的有益效果

Claims (8)

  1. 一种具有抗肿瘤活性的多肽，其特征在于，氨基酸序列为SEQ.ID.NO：1。
  2. 一种具有抗肿瘤活性的多肽，其特征在于，是权利要求1所述多肽的主要功能片段SEQ.ID.NO：2或SEQ.ID.NO：3；或者为SEQ.ID.NO：2和SEQ.ID.NO：3的单个或多个重复序列经过串联、分支或环化而得到的多肽分子序列。
  3. 一种具有抗肿瘤活性的多肽，其特征在于，对权利要求1和2所述多肽进行替换、缺失或***单个或多个氨基酸所得到的衍生多肽，其与权利要求1或2所述多肽序列相似度达到90％或以上。
  4. 一种具有抗肿瘤活性的多肽，其特征在于，其氨基酸序列包括权利要求1至3所述的多肽序列，同时包括其它多肽序列的嵌合肽。
  5. 一种经过生物和化学基团修饰的肽，其特征在于，含有如权利要求1至3所述多肽作为核心序列的C端，或N端，或侧链基团上加PEG修饰或其他分子基团共价修饰的结构特征分子。
  6. 一种编码如权利要求1所述多肽的编码基因，其特征在于，核苷酸序列为SEQ.ID.NO：4。
  7. 如权利要求1至5所述的多肽在制备抗肿瘤药物中的应用。
  8. 如权利要求6所述的多肽的编码基因在制备抗肿瘤药物中的应用。
PCT/CN2019/074726 2019-03-10 2019-03-10 一种抗肿瘤多肽及其应用 WO2020181402A1 (zh)

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PCT/CN2019/074726 WO2020181402A1 (zh) 2019-03-10 2019-03-10 一种抗肿瘤多肽及其应用

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PCT/CN2019/074726 WO2020181402A1 (zh) 2019-03-10 2019-03-10 一种抗肿瘤多肽及其应用

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WO2020181402A1 true WO2020181402A1 (zh) 2020-09-17

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103917243A (zh) * 2011-10-17 2014-07-09 海莱乌医院 基于pd-l1的免疫疗法
CN106832002A (zh) * 2017-02-16 2017-06-13 上海科医联创生物科技有限公司 一种靶向pd‑1的融合蛋白及其相关应用
CN107353326A (zh) * 2017-05-09 2017-11-17 中山大学附属口腔医院 结合pd‑1受体的非抗体结合蛋白及其应用
CN107459559A (zh) * 2017-06-20 2017-12-12 国家纳米科学中心 一种肿瘤免疫治疗预测生物标志物pd‑l1靶向多肽及其应用
WO2017220602A1 (en) * 2016-06-21 2017-12-28 Herlev Hospital Pdl1 peptides for use in cancer vaccines
CN107556367A (zh) * 2017-07-13 2018-01-09 国家纳米科学中心 一种肿瘤免疫治疗预测生物标志物pd‑l2靶向多肽及其应用
CN108840923A (zh) * 2018-06-22 2018-11-20 上海交通大学医学院附属仁济医院 一种靶向pd-l1的多肽及其应用
CN109053862A (zh) * 2018-08-07 2018-12-21 复旦大学附属肿瘤医院 靶向PD-L1的多肽衍生物及其99mTc配合物的制备和应用
CN109071639A (zh) * 2015-11-18 2018-12-21 默沙东公司 Pd1/ctla4结合剂

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103917243A (zh) * 2011-10-17 2014-07-09 海莱乌医院 基于pd-l1的免疫疗法
CN109071639A (zh) * 2015-11-18 2018-12-21 默沙东公司 Pd1/ctla4结合剂
WO2017220602A1 (en) * 2016-06-21 2017-12-28 Herlev Hospital Pdl1 peptides for use in cancer vaccines
CN106832002A (zh) * 2017-02-16 2017-06-13 上海科医联创生物科技有限公司 一种靶向pd‑1的融合蛋白及其相关应用
CN107353326A (zh) * 2017-05-09 2017-11-17 中山大学附属口腔医院 结合pd‑1受体的非抗体结合蛋白及其应用
CN107459559A (zh) * 2017-06-20 2017-12-12 国家纳米科学中心 一种肿瘤免疫治疗预测生物标志物pd‑l1靶向多肽及其应用
CN107556367A (zh) * 2017-07-13 2018-01-09 国家纳米科学中心 一种肿瘤免疫治疗预测生物标志物pd‑l2靶向多肽及其应用
CN108840923A (zh) * 2018-06-22 2018-11-20 上海交通大学医学院附属仁济医院 一种靶向pd-l1的多肽及其应用
CN109053862A (zh) * 2018-08-07 2018-12-21 复旦大学附属肿瘤医院 靶向PD-L1的多肽衍生物及其99mTc配合物的制备和应用

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