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一种在HLA - A24前列腺癌患者中具有免疫原性的前列腺干细胞抗原衍生肽。

A prostate stem cell antigen-derived peptide immunogenic in HLA-A24- prostate cancer patients.

作者信息

Matsueda Satoko, Yao Akihisa, Ishihara Yuki, Ogata Rika, Noguchi Masanori, Itoh Kyogo, Harada Mamoru

机构信息

Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

出版信息

Prostate. 2004 Aug 1;60(3):205-13. doi: 10.1002/pros.20038.

Abstract

BACKGROUND

We attempted to identify prostate stem cell antigen (PSCA)-derived peptides immunogenic in HLA-A24+ prostate cancer patients.

METHODS

Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with each of three different PSCA-derived peptides, which were prepared based on the HLA-A24 binding motif, and their peptide-specific and HLA-A24-restricted anti-tumor responses were examined. Plasma levels of immunoglobulin G (IgG) against PSCA peptides were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Among three PSCA peptides, the PSCA 76-84 peptide most effectively induced peptide-specific cytotoxic T lymphocytes (CTLs) from PBMCs of HLA-A24+ prostate cancer patients. Cytotoxicity was dependent on peptide-specific and CD8+ T cells. The PSCA 76-84 peptide-stimulated PBMCs showed a significant level of cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. IgG reactive to the PSCA 76-84 peptide was detected in half of patients.

CONCLUSIONS

The PSCA 76-84 peptide should be considered for use in clinical trials of immunotherapy for HLA-A24+ patients.

摘要

背景

我们试图鉴定在HLA - A24阳性前列腺癌患者中具有免疫原性的前列腺干细胞抗原(PSCA)衍生肽。

方法

用基于HLA - A24结合基序制备的三种不同的PSCA衍生肽分别在体外刺激外周血单个核细胞(PBMC),并检测其肽特异性和HLA - A24限制性抗肿瘤反应。通过酶联免疫吸附测定(ELISA)测量针对PSCA肽的免疫球蛋白G(IgG)的血浆水平。

结果

在三种PSCA肽中,PSCA 76 - 84肽最有效地从HLA - A24阳性前列腺癌患者的PBMC中诱导出肽特异性细胞毒性T淋巴细胞(CTL)。细胞毒性依赖于肽特异性和CD8 + T细胞。PSCA 76 - 84肽刺激的PBMC以HLA - A24限制性方式对前列腺癌细胞表现出显著水平的细胞毒性。在一半的患者中检测到对PSCA 76 - 84肽有反应的IgG。

结论

对于HLA - A24阳性患者的免疫治疗临床试验,应考虑使用PSCA 76 - 84肽。

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