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

Info

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
Authority
WO
WIPO (PCT)
Prior art keywords
polypeptide
tumor
seq
sequence
tumor activity
Prior art date
Application number
PCT/CN2019/074726
Other languages
English (en)
French (fr)
Inventor
胡西木
Original Assignee
胡西木
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 胡西木 filed Critical 胡西木
Priority to PCT/CN2019/074726 priority Critical patent/WO2020181402A1/zh
Publication of WO2020181402A1 publication Critical patent/WO2020181402A1/zh

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/08Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic 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.

Landscapes

  • 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、缺失或插入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)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/074726 WO2020181402A1 (zh) 2019-03-10 2019-03-10 一种抗肿瘤多肽及其应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/074726 WO2020181402A1 (zh) 2019-03-10 2019-03-10 一种抗肿瘤多肽及其应用

Publications (1)

Publication Number Publication Date
WO2020181402A1 true WO2020181402A1 (zh) 2020-09-17

Family

ID=72426803

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/074726 WO2020181402A1 (zh) 2019-03-10 2019-03-10 一种抗肿瘤多肽及其应用

Country Status (1)

Country Link
WO (1) WO2020181402A1 (zh)

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
CN109071639A (zh) * 2015-11-18 2018-12-21 默沙东公司 Pd1/ctla4结合剂
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

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

Similar Documents

Publication Publication Date Title
RU2020113032A (ru) Новые пептиды и комбинации пептидов для применения в иммунотерапии рака легких, в том числе немелкоклеточного рака легких (нмрл) и других видов рака
JP6243452B2 (ja) アルブミン結合アルギニンデイミナーゼ融合たんぱく質を含有する医薬組成物
JP2010540453A5 (zh)
RU2018101710A (ru) Мутации фермента crispr, уменьшающие нецелевые эффекты
US9757473B2 (en) Cell-penetrating peptide and conjugate comprising same
JP2015512246A5 (zh)
DE69834824D1 (de) Nukleinsäure, welche einen von lektin abstammenden faktor zur präservierung von progenitorzellen kodiert
KR101310511B1 (ko) 흉선-특이성 단백질
WO2006085583A1 (ja) 細胞透過性ペプチド
JP2018512124A5 (zh)
US20180291114A1 (en) Recombinant bi-specific polypeptide for coordinately activating tumor-reactive t-cells and neutralizing immune suppression
WO2013003987A1 (zh) 一种肿瘤靶向性肿瘤坏死因子相关凋亡配体变体及其应用
CN104311672B (zh) 一种具有肿瘤细胞靶向性的抑制剂多肽
JP2010521441A5 (zh)
CA2532460A1 (en) Synthetic gene encoding human epidermal growth factor 2/neu antigen and uses thereof
KR102166549B1 (ko) 혈뇌장벽 투과성 펩티드 및 이를 포함하는 컨쥬게이트
WO2020181402A1 (zh) 一种抗肿瘤多肽及其应用
CN104558119B (zh) Yap蛋白抑制多肽及其应用
KR102307567B1 (ko) 항염증 활성을 갖는 펩티드 및 이를 포함하는 조성물
JP2012507278A5 (zh)
JP6975716B2 (ja) 樹状細胞標的化ペプチド、当該ペプチドを利用したペプチド融合体、及び当該ペプチド融合体を利用したワクチン
JP2005512509A5 (zh)
CN1517437B (zh) 特异性治疗肿瘤或胞内感染的疫苗及应用
CN113817071B (zh) 一种egfr靶向的trail融合蛋白及其制备方法和用途
CN112480262B (zh) 一种融合蛋白及其制备与应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19919339

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19919339

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 19919339

Country of ref document: EP

Kind code of ref document: A1