Matsueda Satoko, Yao Akihisa, Ishihara Yuki, Ogata Rika, Noguchi Masanori, Itoh Kyogo, Harada Mamoru
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Prostate. 2004 Aug 1;60(3):205-13. doi: 10.1002/pros.20038.
We attempted to identify prostate stem cell antigen (PSCA)-derived peptides immunogenic in HLA-A24+ prostate cancer patients.
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).
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.
The PSCA 76-84 peptide should be considered for use in clinical trials of immunotherapy for HLA-A24+ patients.
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。
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。
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。
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。