Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer.
Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer.
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DOI：
10.1186/1479-5876-7-103
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发表时间：
2009-12-09
影响因子：
7.4
通讯作者：
Sato N
中科院分区：
文献类型：
--
作者：
Honma I;Torigoe T;Hirohashi Y;Kitamura H;Sato E;Masumori N;Tamura Y;Tsukamoto T;Sato N
α -甲基酰基辅酶a消旋酶（AMACR）是一种在支链脂肪酸及其衍生物的β -氧化过程中起重要作用的酶。AMACR在多种癌症中均有高表达，包括前列腺癌、结直肠癌和肾癌。由于其癌症特异性和频繁表达，AMACR可能成为基于细胞毒性t淋巴细胞（CTL）的癌症免疫治疗的一个有吸引力的靶点。在本研究中，我们检测了前列腺癌患者外周血单个核细胞（PBMCs）诱导amacr特异性CTL的情况，并确定了hla - a24限制性CTL表位。RT-PCR和免疫组化分析显示，与良性或正常前列腺组织相比，AMACR在前列腺癌细胞系和组织中表达强烈。从该蛋白的氨基酸序列合成了4个携带HLA-A24结合基序的amacr衍生肽，并分析了它们与HLA-A24的结合亲和力。通过用肽刺激患者的pbmc， 11例患者中有6例成功诱导特异性ctl。在HLA-A24环境下，肽特异性ctl对表达amacr的前列腺癌细胞具有显著的细胞毒活性。我们的研究表明，AMACR可以成为前列腺癌免疫治疗的靶抗原，AMACR衍生的肽可能是hla - a24阳性表达AMACR的癌症患者良好的肽疫苗候选物。
Alpha-methylacyl-CoA racemase (AMACR) is an enzyme playing an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives. High expression levels of AMACR have been described in various cancers, including prostate cancer, colorectal cancer and kidney cancer. Because of its cancer-specific and frequent expression, AMACR could be an attractive target for cytotoxic T-lymphocyte (CTL)-based immunotherapy for cancer. In the present study, we examined the induction of AMACR-specific CTLs from prostate cancer patients' peripheral blood mononuclear cells (PBMCs) and determined HLA-A24-restricted CTL epitopes. RT-PCR and immunohistochemical analysis revealed that AMACR was strongly expressed in prostate cancer cell lines and tissues as compared with benign or normal prostate tissues. Four AMACR-derived peptides carrying the HLA-A24-binding motif were synthesized from the amino acid sequence of this protein and analyzed to determine their binding affinities to HLA-A24. By stimulating patient's PBMCs with the peptides, specific CTLs were successfully induced in 6 of 11 patients. The peptide-specific CTLs exerted significant cytotoxic activity against AMACR-expressing prostate cancer cells in the context of HLA-A24. Our study demonstrates that AMACR could become a target antigen for prostate cancer immunotherapy, and that the AMACR-derived peptides might be good peptide vaccine candidates for HLA-A24-positive AMACR-expressing cancer patients.
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影响因子：
82.9
作者：
Rosenberg, SA;Yang, JC;White, DE
通讯作者：
White, DE
影响因子：
5.8
作者：
Alves, Pedro M. S.;Faure, Olivier;Kosmatopoulos, Kostas
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影响因子：
2.1
作者：
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STERN, PL
影响因子：
6.6
作者：
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通讯作者：
RATLIFF, TL
影响因子：
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作者：
Date, Y;Kimura, A;Sasazuki, T
通讯作者：
Sasazuki, T