Uenaka Akiko, Wada Hisashi, Isobe Midori, Saika Takashi, Tsuji Kazuhide, Sato Eiichi, Sato Shuichiro, Noguchi Yuji, Kawabata Ryohei, Yasuda Takushi, Doki Yuichiro, Kumon Hiromi, Iwatsuki Keiji, Shiku Hiroshi, Monden Morito, Jungbluth Achim A, Ritter Gerd, Murphy Roger, Hoffman Eric, Old Lloyd J, Nakayama Eiichi
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan.
Cancer Immun. 2007 Apr 19;7:9.
We recently showed that vaccination with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP-NY-ESO-1) elicited antibody responses in 9 of 9 patients vaccinated in a clinical trial. In this study, we performed T cell immunomonitoring and analyzed tumor responses in these patients. To evaluate CD4 and CD8 T cell responses, an IFN-gamma secretion assay was used. The assay showed low background and was sensitive for detecting antigen-specific T cells. An increase in the CD4 T cell response was observed in 2 of 2 initially sero-positive and 5 of 7 initially sero-negative patients after vaccination. An increase in the CD8 T cell response was also observed in 2 of 2 sero-positive and 5 of 7 sero-negative patients after vaccination. Analysis of peptides recognized by CD4 and CD8 T cells revealed two dominant NY-ESO-1 regions, 73-114 and 121-144. Tumor responses were observed in 3 esophageal cancer patients and a malignant melanoma patient. In 3 of 4 prostate cancer patients, prostate-specific antigen (PSA) values stabilized during the course of vaccination. The use of whole protein, containing multiple CD4 and CD8 epitopes, may be beneficial for cancer vaccines to prevent tumors from evading the immune response.
我们最近发现，在一项临床试验中，用含胆固醇的疏水化普鲁兰多糖与NY-ESO-1蛋白复合物（CHP-NY-ESO-1）进行疫苗接种，9名接种患者中有9名产生了抗体反应。在本研究中，我们对这些患者进行了T细胞免疫监测并分析了肿瘤反应。为评估CD4和CD8 T细胞反应，采用了γ干扰素分泌试验。该试验背景值低，对检测抗原特异性T细胞敏感。接种疫苗后，2名初始血清阳性患者中的2名以及7名初始血清阴性患者中的5名观察到CD4 T细胞反应增加。接种疫苗后，2名血清阳性患者中的2名以及7名血清阴性患者中的5名也观察到CD8 T细胞反应增加。对CD4和CD8 T细胞识别的肽段分析显示，NY-ESO-1有两个主要区域，即73-114和121-至144。3名食管癌患者和1名恶性黑色素瘤患者出现了肿瘤反应。在4名前列腺癌患者中的3名，接种疫苗过程中前列腺特异性抗原（PSA）值保持稳定。使用含有多个CD4和CD8表位的全蛋白，可能有助于癌症疫苗预防肿瘤逃避免疫反应。
