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）是一种主要在前列腺癌中表达的跨膜糖蛋白，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 HLA-A24 限制性表位肽，以进一步应用针对前列腺癌的基于树突状细胞 (DC) 的免疫疗法，我们筛选了几种 PSMA 编码的 HLA-A24 结合肽，以确定其诱导特异性抗肿瘤细胞毒性 T- 的能力。淋巴细胞（CTL）体外反应。研究了总共 9 种肽是否可以通过使用来自 HLA-A24+健康供体的外周血单核细胞的预肽注射的自体 DC 作为抗原呈递细胞对 CD8+ T 细胞进行初次体外免疫来引发 CTL 应答。两种肽，Lysdpadyf 和 NYATEDFF，被鉴定能够引发 CLT 系，该系裂解用每种肽脉冲的 HLA-A24+靶细胞。使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 代和抗 CD8 单克隆抗体 (mAB)，但不是抗 MHC II 类和抗 CD4mAB。这些新型 HLA-A-24 限制性 PSMA 表位肽的鉴定将为我们提供进一步评估基于 DC 的针对激素难治性前列腺癌的免疫治疗策略的临床可行性的机会。