Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patients

Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patients
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DOI:
10.1002/ijc.22583
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发表时间:
2007-05-15
影响因子:
6.4
通讯作者:
Nakayama, Eiichi
Nakayama, Eiichi
中科院分区:
医学1区
文献类型:
--
作者:
Kawabata, Ryohei;Wada, Hisashi;Nakayama, Eiichi

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NY-ESO-1特异性体液应答经常在各种类型的NY-ESO-1抗原表达肿瘤患者中观察到。在大比例的NY-ESO-1抗体阳性患者中,也可以检测到NY-ESO-1特异性CD 8 T细胞,这表明监测NY-ESO-1特异性体液免疫应答可能是临床疫苗研究中估计针对NY-ESO-1的总体免疫应答的相关且更实用的替代物。我们用含胆固醇的疏水化普鲁兰配制的全长NY-ESO-1蛋白(CHP-NY-ESO-1)免疫了9名癌症患者,并研究了针对NY-ESO-1的体液免疫反应。接种前,7例患者为NY-ESO-1抗体阴性,2例患者为阳性。用CHP-NY-ESO-1疫苗接种导致所有9名免疫患者中NY-ESO-1抗体应答的诱导或增加。抗原表位分析显示NY-ESO-1蛋白分子中有5个区域被接种后诱导的抗体识别。这5个区域也被未接种疫苗的NY-ESO-1抗体阳性癌症患者中存在的抗体识别。跨越氨基酸91-108的肽在9名接种疫苗的患者中的6名和9名未接种疫苗的血清阳性患者中的8名中被识别,是NY-ESO-1中用于癌症患者中抗体识别的最主要抗原表位。总之,我们表明,CHP-NY-ESO-1蛋白疫苗接种具有在癌症患者中诱导针对NY-ESO-1抗原的体液免疫应答的有效活性。在接种疫苗的患者中抗体识别的抗原表位与具有针对NY-ESO-1的自发体液免疫的癌症患者中识别的抗原表位相似。(c)2007 Wiley-Liss,Inc.
NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY-ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody-negative and 2 patients were positive prior to vaccination. Vaccination with CHP-NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO-1 anti body-positive cancer patients. A peptide spanning amino acids 91-108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO-1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1. (c) 2007 Wiley-Liss, Inc.