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

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。

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.