Identification of SART3-derived peptides having the potential to induce cancer-reactive cytotoxic T lymphocytes from prostate cancer patients with HLA-A3 supertype alleles
Identification of SART3-derived peptides having the potential to induce cancer-reactive cytotoxic T lymphocytes from prostate cancer patients with HLA-A3 supertype alleles
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DOI：
10.1007/s00262-006-0216-9
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
Harada, Mamoru
中科院分区：
文献类型：
--
作者：
Minami, Takafumi;Matsueda, Satoko;Harada, Mamoru
为了扩大抗癌疫苗的可能性，目前最受关注的候选多肽疫苗是人类白细胞抗原A2和人类白细胞抗原A24等位基因，因此，为了扩大抗癌疫苗的可能性，我们鉴定了适用于携带人类白细胞抗原A3超型等位基因的前列腺癌患者的SART3衍生多肽。根据人类白细胞抗原-A3超型等位基因(HLA-A11、-A31和-A33)的结合基序制备的29个SART3衍生肽首先被前列腺癌患者的免疫球蛋白G(Ig G)识别，然后检测其诱导人类白细胞抗原-A3超型(+)前列腺癌患者的多肽特异性细胞毒性T淋巴细胞(CTL)的能力。结果发现，5个SART3多肽能被免疫球蛋白识别，其中2个SART3(511-519)和SART3(734-742)能有效地诱生多肽特异性和抗癌活性CTL。它们对前列腺癌细胞的杀伤作用归因于多肽特异性T细胞和CD8(+)T细胞。这些结果表明，这两个SART3多肽可能成为治疗人类白细胞抗原A3超型(+)前列腺癌患者的多肽免疫治疗的候选分子。
SART3-derived peptides applicable to prostate cancer patients with HLA-A3 supertype alleles were identified in order to expand the possibility of an anti-cancer vaccine, because the peptide vaccine candidates receiving the most attention thus far have been the HLA-A2 and HLA-A24 alleles. Twenty-nine SART3-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were first screened for their recognizability by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific cytotoxic T lymphocytes (CTLs) from HLA-A3 supertype(+) prostate cancer patients. As a result, five SART3 peptides were frequently recognized by IgG, and two of them-SART3 (511-519) and SART3 (734-742)-efficiently induced peptide-specific and cancer-reactive CTLs. Their cytotoxicity toward prostate cancer cells was ascribed to peptide-specific and CD8(+) T cells. These results indicate that these two SART3 peptides could be promising candidates for peptide-based immunotherapy for HLA-A3 supertype(+) prostate cancer patients.