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HLA restricted tumor specific antigen epitope pulsed autologous dendritic cell vaccine treatment for hormone refractory prostate cancer

HLA限制性肿瘤特异性抗原表位脉冲自体树突状细胞疫苗治疗激素难治性前列腺癌

基本信息

批准号：
12671557
负责人：
TACHIBANA Masaaki
金额：
$ 2.56万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671557/
关键词：
Prostate cancer PSMA HLA-A24 epitope peptide dendritic cells treatment ワクチン治療免疫細胞治療

项目摘要

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein predominantly expressed in prostate cancer, is an attractive target for tumor-specific immunotherapy. To identify HLA-A24-restricted epitope peptides from PSMA for further application of the dendritic cells (DC)-based immunotherapy targeting prosate cancer, we have screened several PSMA-encoded HLA-A24 binding peptides for their capabilities to elicit specific antitumor cytotoxic T-lymphocytes (CTL) response in vitro. A total of 9 peptides were studied if they could elicit CTL responses by primary in vitro immunization of CD8+ T cells using preptide-pusled autologous DC derived from peripheral blood mononuclear cells of HLA-A24+Healthy donor as antigen-presenting cells. Two peptides, Lysdpadyf and NYATEDFF, were indentified to be able to elicit CLT lines that lysed HLA-A24+target cells pulsed with each peptides. The antigen specificity of the CTL lines was confirmed utilizing several tumor cell lines as target cells, which were gen I and anti-CD8 monoclonal antibdies (mABs) bur not by anti-MHC class II and anti-CD4mABs. The identification of these novel HLA-A-24-restricted PSMA epitope peptides would provide us the opportunity to further evaluate the clinical feasibility of DC-based immunotherapeutic strategy against hormone-refractory prostate cancers.

前列腺特异性膜抗原（PSMA）是一种在前列腺癌中主要表达的跨膜糖蛋白，是肿瘤特异性免疫治疗的一个有吸引力的靶点。为了从PSMA中鉴定出HLA-A24限制性表位肽，以便进一步应用于基于树突状细胞（DC）的前列腺癌免疫治疗，我们筛选了几种PSMA编码的HLA-A24结合肽，以研究它们在体外引发特异性抗肿瘤细胞毒性t淋巴细胞（CTL）反应的能力。利用HLA-A24+健康供者外周血单个核细胞制备的预肽驱动的自体DC作为抗原提呈细胞，研究了9种多肽是否能通过体外原代免疫CD8+ T细胞引起CTL反应。两种肽，Lysdpadyf和NYATEDFF，被鉴定出能够诱导CLT细胞系裂解HLA-A24+靶细胞。利用几种肿瘤细胞系作为靶细胞，证实了CTL系的抗原特异性，这些肿瘤细胞系是I类和抗cd8单克隆抗体，而不是抗mhc II类和抗cd4单克隆抗体。这些新的hla - a -24限制性PSMA表位肽的鉴定将为我们进一步评估基于dc的免疫治疗策略治疗激素难治性前列腺癌的临床可行性提供机会。