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Detection of IgG antibody reactive to a p53-derived peptide with HLA-A4601 binding motif in breast cancer patients

检测乳腺癌患者中与带有 HLA-A4601 结合基序的 p53 衍生肽有反应的 IgG 抗体

基本信息

批准号：
16591281
负责人：
SHICHIJO Shigeki
金额：
$ 2.18万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Purpose : We previously reported the existence of p53-derived non-mutated peptides as cytotoxic T lymphocyte(CTL) epitopes in breast cancer(BC) patients(Ref.11). We also demonstrated that Ab reactive to CTL epitope peptides can be used as a laboratory marker to predict better estimate the prognosis of cancer patients receiving peptide vaccinations(Ref.14). The object of this study was to better understand the immune responses to p53-peptides in BC patients. Experimental Design : We measured anti-p53-peptides in the sera of patients with BC(n=104), prostate cancer(PC, n=50), autoimmune diseases(AI, n=50), atopic disease(AD, n=24), and healthy donors(HDs, n=83). Result : The levels of IgG specific to the p53377-385 in both BC and Al patients were significantly higher than those in AD, PC, and HDs. Significant levels of the anti-p53377-385 IgG were detected in the sera from 23% of the patients with BC, 0% with PC, 32% with AI, 4% with AD, and 5% HDs. Anti-p53377-385 activity in the sera was largely reduced by absorption with the corresponding peptide, but not with the entire p53-protein. IgG reactive to entire p53-protein was detectable in the sera from 12 BC patients(12%), and only 4 of those patients were positive for anti-p53377-385 IgG. As regards prognosis, this anti-peptide Ab did not correlate with a poor prognosis, but rather seemed to be associated with a good prognosis of these BC patients in terms of stage, invasion of tumor cells, and recurrence. Conclusions : These results may provide new insight to achieve a better understanding of the immune responses to p53 antigen at the peptide level in BC patients.

目的：我们之前报道了p53衍生的非突变肽作为乳腺癌（BC）患者的细胞毒性T淋巴细胞（CTL）表位的存在（参考文献11）。我们还证明，抗体对CTL表位肽的反应可以作为实验室标记物，更好地预测接受肽疫苗接种的癌症患者的预后（参考文献14）。本研究的目的是为了更好地了解BC患者对p53肽的免疫反应。实验设计:我们测量anti-p53-peptides在公元前患者的血清(n = 104)、前列腺癌(PC, n = 50),自身免疫性疾病(AI, n = 50),过敏性疾病(广告,n = 24),和健康的捐助者(HDs, n = 83)。结果：BC和Al患者p53377-385特异性IgG水平明显高于AD、PC和hd患者。23%的BC患者、0%的PC患者、32%的AI患者、4%的AD患者和5%的hd患者血清中检测到显著水平的抗p53377-385 IgG。血清中抗p53377-385的活性被相应肽的吸收大大降低，但不被整个p53蛋白吸收。在12例BC患者（12%）的血清中检测到对整个p53蛋白反应的IgG，其中只有4例患者的抗p53377-385 IgG阳性。至于预后，这种抗肽Ab与不良预后无关，而似乎与这些BC患者的分期、肿瘤细胞侵袭和复发的良好预后有关。结论:这些结果可能会提供新的见解达到更好地了解p53免疫反应的抗原肽水平在公元前的病人。