Thurner B, Haendle I, Röder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von den Driesch P, Bröcker E B, Steinman R M, Enk A, Kämpgen E, Schuler G
Department of Dermatology, University of Erlangen-Nuremberg, D-91052 Erlangen, Germany.
J Exp Med. 1999 Dec 6;190(11):1669-78. doi: 10.1084/jem.190.11.1669.
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 x 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 10(6) and 12 x 10(6) 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.
树突状细胞（DCs）被认为是诱导癌症免疫的有前景的佐剂。我们使用成熟的、单核细胞来源的DCs来引发对恶性黑色素瘤的抗性。DCs用Mage - 3A1肿瘤肽和一种回忆抗原、破伤风类毒素或结核菌素进行脉冲处理。11例尽管接受了标准化疗仍病情进展的晚期IV期黑色素瘤患者，每隔14天接受5次DC疫苗接种。前三次疫苗接种通过皮下和皮内注射，每次3×10⁶个DCs，随后分别进行两次静脉注射，每次6×10⁶和12×10⁶个DCs。仅观察到轻微（小于或等于II级）的副作用。对回忆抗原的免疫得到增强。8/11的患者中诱导出了Mage - 3A1特异性CD8⁺细胞毒性T淋巴细胞（CTL）前体的显著扩增。奇怪的是，这些免疫反应在静脉接种疫苗后常常下降。6/11的患者中可见单个转移灶（皮肤、淋巴结、肺和肝）的消退。两名患者皮肤转移灶的消退伴随着红斑和CD8⁺T细胞浸润，而未消退的病灶缺乏CD8⁺T细胞以及Mage - 3 mRNA表达。本研究证明了DC“疫苗”即使在晚期癌症中也能频繁扩增肿瘤特异性CTL并引发消退这一原理，此外，还为原位活跃的CD8⁺CTL - 肿瘤细胞相互作用以及因缺乏肿瘤抗原表达而导致的逃逸提供了证据。
