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首页> 美国卫生研究院文献>The Journal of Experimental Medicine >Vaccination with Mage-3a1 Peptide–Pulsed Mature Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
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Vaccination with Mage-3a1 Peptide–Pulsed Mature Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma

机译：用Mage-3a1肽冲动的成熟单核细胞衍生树突状细胞接种疫苗可扩展特定的细胞毒性T细胞并诱导晚期IV期黑素瘤某些转移的消退。

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Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8+ cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8+ T cell infiltration, whereas nonregressing lesions lacked CD8+ T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression.
机译：树突状细胞（DC）被认为是诱导癌症免疫的有前途的佐剂。我们使用成熟的单核细胞来源的DC引发对恶性黑色素瘤的抵抗。用Mage-3A1肿瘤肽和召回抗原，破伤风类毒素或结核菌素对DC脉冲。尽管采用标准化学疗法但仍进展性的11例晚期IV期黑色素瘤患者每隔14天接受了5次DC疫苗接种。头三剂疫苗注射入皮肤，皮下和皮内分别注射3×10 6 DC，然后两次静脉注射6×10 6 和12×10 6 个DC。仅观察到轻微的副作用（小于或等于II级）。召回抗原的免疫力增强。在8/11例患者中，诱导了Mage-3A1特异性CD8 + 细胞毒性T淋巴细胞（CTL）前体的显着扩增。奇怪的是，静脉注射疫苗后，这些免疫反应通常会下降。在6/11患者中，单个转移灶（皮肤，淋巴结，肺和肝）的消退明显。两名患者皮肤转移的消退伴有红斑和CD8 + T细胞浸润，而非退行性病变缺乏CD8 + T细胞以及Mage-3 mRNA表达。这项研究证明了原理，即DC“疫苗”即使在晚期癌症中也能经常扩展肿瘤特异性CTLs并引起消退，此外，它为CD8 + CTL-肿瘤细胞在原位活跃的相互作用提供了证据。以及由于缺乏肿瘤抗原表达而逃脱。

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