基于化学合成疫苗的肿瘤免疫疗法
详细信息 查看官网全文
- 英文论文题名：Chemical Synthetic Vaccine for Cancer Immunotherapy
- 论文作者：李艳梅
- 英文论文作者：Yan-Mei Li ; Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology(Ministry of Education) Department of Chemistry Tsinghua University
- 年：2016
- 作者机构：清华大学化学系生命有机磷化学及化学生物学教育部重点实验室;
- 论文关键词：抗肿瘤疫苗 ; MUC1糖肽 ; 化学合成
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：R730.51
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：182k
- 原文格式：D
- 会议级别：全国
摘要
近年来,化学合成抗肿瘤疫苗由于其安全有效、组分均一、副作用小等特点,被视作是癌症免疫疗法的新思路。MUC1粘蛋白是一种大量表达于肿瘤细胞表面的大分子量糖蛋白,其胞外区含有大量20个氨基酸残基的串联重复序列。被肿瘤相关糖抗原修饰的MUC1糖肽被看作是很好的肿瘤抗原靶标,但由于低免疫原性,需要各种不同策略来构建化学合成抗肿瘤疫苗。首先,我们将MUC1糖肽与载体蛋白共价偶联形成抗肿瘤疫苗,通过免疫评价筛选出最佳抗原表位~([1])。但载体蛋白免疫原性很强,会引起严重副作用。我们筛选出破伤风毒素中的辅助T细胞表位,与MUC1糖肽偶联形成两组分疫苗~([2])。我们进一步构建了含有MUC1糖肽、辅助T细胞表位和具有佐剂效应的Toll样受体2的激动剂(Pam_3CSK_4脂肽)的三组分疫苗~([3-4]),该疫苗可引起小鼠很强的免疫反应。此外,基于免疫簇效应和尺寸效应,我们设计了含有多个MUC1糖肽和Pam_3CSK_4脂肽缀合的多价疫苗~([5]),多肽自组装无佐剂疫苗~([6])和层层自组装纳米疫苗~([7])。这些疫苗分子都能刺激小鼠免疫系统,产生抗原特异性免疫反应。
Chemical synthetic antitumor vaccine is very promising for cancer immunotherapy,because of the effectivity,safety,homogeneous components et al.MUC1 is an over-expressed glycoprotein on cancer cell membrane with variable number of tandem repeats on the extracellular domain.The MUC1 glycopeptide bearing with tumor-associated carbohydrate antigen is proved to be a good epitope for constructing vaccines.However,due to the weak immunogenicity of MUC1 glycoeptide,many strategies should be taken.Firstly,we conjugated MUC1 glycopeptide with carrier protein to form antitumor vaccines.However,carrier proteins are very immunogenic,so we separated the helper T cell epitope from Tetanus Toxoid and conjugated with MUC1 glycopeptide to construct two-component vaccines.To further improve the effects of vaccines,a three-component vaccine was constructed,which contains MUC1 glycopeptide,helper T cell epitope and the immune-stimulator Pam_3CSK_4 lipopeptide.Besides,we constructed multivalent vaccines,adjuvant-free vaccines based on self-assembly peptides and nano-vaccines based on layer-by-layer self-assembly.These vaccines could stimulate immune system and elicit antigen specific immune responses.
Chemical synthetic antitumor vaccine is very promising for cancer immunotherapy,because of the effectivity,safety,homogeneous components et al.MUC1 is an over-expressed glycoprotein on cancer cell membrane with variable number of tandem repeats on the extracellular domain.The MUC1 glycopeptide bearing with tumor-associated carbohydrate antigen is proved to be a good epitope for constructing vaccines.However,due to the weak immunogenicity of MUC1 glycoeptide,many strategies should be taken.Firstly,we conjugated MUC1 glycopeptide with carrier protein to form antitumor vaccines.However,carrier proteins are very immunogenic,so we separated the helper T cell epitope from Tetanus Toxoid and conjugated with MUC1 glycopeptide to construct two-component vaccines.To further improve the effects of vaccines,a three-component vaccine was constructed,which contains MUC1 glycopeptide,helper T cell epitope and the immune-stimulator Pam_3CSK_4 lipopeptide.Besides,we constructed multivalent vaccines,adjuvant-free vaccines based on self-assembly peptides and nano-vaccines based on layer-by-layer self-assembly.These vaccines could stimulate immune system and elicit antigen specific immune responses.
引文
[1]Cai,H.;Huang,Z.H.;Kunz,H.;Li,Y.M.Angew.Chem.Int.Ed.2012,51,1719-1723
[2]Cai,H.;Chen,M.S.;Kunz,H.;Li,Y.M.Angew.Chem.Int.Ed.2013,52,6106-6110.
[3]Cai,H.;Sun,Z.Y.;Kunz,H.;Li,Y.M.Chem.-Eur.J.2013,19,1962-1970.
[4]Gao,Y.;Sun,Z.Y.;Zhao,Y.F.;Li,Y.M.Chem.-Eur.J.2014,20,13541-13546.
[5]Cai,H.;Sun,Z.Y.;Kunz,H.;Li,Y.M.Angew.Chem.Int.Ed.2014,53,1699-1703.
[6]Huang,Z.H.;Shi,L.;Zhao,Y.F.;Li,Y.M.J.Am.Chem.Soc.2012,134,8730-8733.
[7]Liu,Y.F.;Sun,Z.Y.;Chen.Y.X.;Li,Y.M.Bioconjugate Chem.2015,26,1439-1442.
[2]Cai,H.;Chen,M.S.;Kunz,H.;Li,Y.M.Angew.Chem.Int.Ed.2013,52,6106-6110.
[3]Cai,H.;Sun,Z.Y.;Kunz,H.;Li,Y.M.Chem.-Eur.J.2013,19,1962-1970.
[4]Gao,Y.;Sun,Z.Y.;Zhao,Y.F.;Li,Y.M.Chem.-Eur.J.2014,20,13541-13546.
[5]Cai,H.;Sun,Z.Y.;Kunz,H.;Li,Y.M.Angew.Chem.Int.Ed.2014,53,1699-1703.
[6]Huang,Z.H.;Shi,L.;Zhao,Y.F.;Li,Y.M.J.Am.Chem.Soc.2012,134,8730-8733.
[7]Liu,Y.F.;Sun,Z.Y.;Chen.Y.X.;Li,Y.M.Bioconjugate Chem.2015,26,1439-1442.