II. Medizinische Klinik, Hämatologie - Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Clin Cancer Res. 2011 Feb 15;17(4):861-70. doi: 10.1158/1078-0432.CCR-10-1811. Epub 2010 Dec 16.
NY-ESO-1, one of the most immunogenic tumor antigens, is expressed in 15% to 25% of metastatic prostate cancers. The immunological and clinical effects of vaccination with recombinant NY-ESO-1 protein combined with CpG as adjuvant were evaluated.
In a phase I clinical study, patients with advanced prostate cancer were vaccinated with recombinant NY-ESO-1 protein (100 μg) mixed with CpG 7909 (2.5 mg) every 3 weeks intradermally for 4 doses. Objectives of the study were the safety of the vaccine and changes of specific humoral and cellular immunological responses to NY-ESO-1 in relation to detectable NY-ESO-1 expression in the individual tumor.
All 12 baseline sero-negative patients developed high-titer NY-ESO-1 antibody responses. B-cell epitope mapping identified NY-ESO-1 p91-110 to be recognized most frequently by vaccine-induced antibodies. Two patients developed significant antibody titers against the adjuvant CpG. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were induced in 9 patients (69%). Five of these 9 patients did not express NY-ESO-1 in the autologous tumor. Postvaccine CD8+ T-cell clones recognized and lyzed HLA-matched tumor cell lines in an antigen-specific manner.
Our data provide clear evidence for the capacity of NY-ESO-1 protein/CpG vaccine to induce integrated antigen-specific immune responses in vivo and to efficiently prime CD8+ T-cell responses in NY-ESO-1 antigen-negative patients. Our results may also support further clinical vaccination protocols with NY-ESO-1 protein not only focused on the treatment of existing cancer, but also to prevent further development of NY-ESO-1 positive cancers in vivo.
NY-ESO-1 是最具免疫原性的肿瘤抗原之一，在 15%至 25%的转移性前列腺癌中表达。评估了用重组 NY-ESO-1 蛋白联合 CpG 作为佐剂进行疫苗接种的免疫和临床效果。
在一项 I 期临床研究中，用重组 NY-ESO-1 蛋白（100μg）与 CpG 7909（2.5mg）混合，每 3 周皮内注射 4 剂，对晚期前列腺癌患者进行疫苗接种。研究的目的是疫苗的安全性，以及个体肿瘤中可检测到的 NY-ESO-1 表达与 NY-ESO-1 特异性体液和细胞免疫反应变化之间的关系。
所有 12 例基线血清阴性患者均产生高滴度的 NY-ESO-1 抗体反应。B 细胞表位作图确定 NY-ESO-1 p91-110 是疫苗诱导抗体最常识别的表位。两名患者对佐剂 CpG 产生了显著的抗体滴度。9 名患者（69%）诱导产生了 NY-ESO-1 特异性 CD4+和/或 CD8+T 细胞反应。这 9 名患者中的 5 名在自体肿瘤中不表达 NY-ESO-1。疫苗接种后 CD8+T 细胞克隆以抗原特异性方式识别和裂解 HLA 匹配的肿瘤细胞系。
我们的数据提供了明确的证据，证明 NY-ESO-1 蛋白/CpG 疫苗能够在体内诱导整合的抗原特异性免疫反应，并有效地在 NY-ESO-1 抗原阴性患者中诱导 CD8+T 细胞反应。我们的结果也可能支持进一步的 NY-ESO-1 蛋白临床疫苗接种方案，不仅针对现有癌症的治疗，还针对体内 NY-ESO-1 阳性癌症的进一步发展。
