Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide
Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide
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DOI：
10.1007/s00262-005-0090-x
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发表时间：
2006-09-01
影响因子：
5.8
通讯作者：
Peace, David J.
中科院分区：
文献类型：
--
作者：
Perambakam, Supriya;Hallmeyer, Sigrun;Peace, David J.
前列腺癌（CaP）的T细胞免疫疗法提供了毒性更小，更有效的结果的潜力。在28名患有局部晚期或转移性CaP的患者中进行临床试验，以确定前列腺特异性抗原PSA 146 -154（PSA肽）的HLA-A2结合表位是否可以诱导特异性T细胞免疫。在第1、4和10周，通过皮内注射PSA肽和GM-CSF或静脉内施用用PSA肽脉冲的自体树突状细胞，对患者进行疫苗接种。在第4、14、26和52周进行迟发型超敏反应（DTH）皮肤试验。50%的患者对PSA肽产生了阳性DTH反应。在大多数有反应的患者中，DTH硬结的大小随着时间的推移而逐渐增加。从七个DTH阳性患者的皮肤活检和原位开发的T细胞也进行了表征。回收的T细胞的表型表现出不同比例的CD 4（+）CD 8（-）、CD 4（-）stopCD 8（+）stop和CD 4（+）CD 8（+）T细胞群。PSA-肽刺激的T细胞的细胞因子分析每珠阵列测定在七名患者中的六名中表现出特异性IFN-γ和TNF-α应答。在5例患者中观察到特异性IL-4应答，而在1例患者中检测到IL-10应答。从4名患者中分离的纯化的CD 4（-）CD 8（+）T细胞经铬释放试验证明具有特异性细胞溶解活性。总之，免疫与PSA肽诱导特异性T细胞免疫的一半的患者与局部晚期和肿瘤敏感性，转移性CaP。DTH衍生的T细胞表现出PSA肽特异性细胞溶解活性，并主要表达1型细胞因子谱。
T cell immunotherapy of prostate cancer (CaP) offers the potential for less toxic, more effective outcomes. A clinical trial was conducted in 28 patients with locally advanced or metastatic CaP to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed-type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. The size of the DTH induration progressively increased over time in the majority of responding patients. Skin biopsies from seven DTH-positive patients were available and T cells that developed in situ were also characterized. The phenotype of recovered T cells demonstrated variable proportions of CD4(+) CD8(-), CD4(-) stopCD8(+) stop and CD4(+) CD8(+) T cell populations. Cytokine analysis of PSA-peptide stimulated T cells per bead array assay exhibited specific IFN-gamma and TNF-alpha response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4(-) CD8(+) T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. In conclusion, immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile.