Wei Yanzhang, Sticca Robert P, Holmes Lillia M, Burgin Kelly E, Li Jinhua, Williamson Jane, Evans Lyndon, Smith Samuel J, Stephenson Joseph J, Wagner Thomas E
Oncology Research Institute and the Cancer Treatment Center, Greenville Hospital System, Greenville, SC 29605, USA.
Int J Oncol. 2006 Mar;28(3):585-93.
A pilot clinical trial using dendritomas, purified hybrids from the fusion of dendritic/tumor cells combined with a low dose of IL-2, in metastatic melanoma patients was conducted in order to determine its safety and potential immunological and clinical responses. Ten metastatic melanoma patients were enrolled into this study. Dendritoma vaccines were created by fusing dendritic cells stained with green fluorescent dye with irradiated autologous tumor cells stained with red fluorescent dye and purifying the hybrids using immediate fluorescent-activated cell sorting. Initial vaccine was given subcutaneously and followed by IL-2 in serially elevated doses from 3-9 million units/m2 for 5 days. Repeated vaccinations were administered without IL-2, at 3-month intervals for a maximum of 5 times. Immune reactions were measured by the increase of interferon-gamma (IFN-gamma) expressing T cells. Vaccine doses ranged from 250,000 to 1,000,000 dendritomas. There was no grade 2 or higher toxicity directly attributable to the vaccine. All patients experienced toxicity due to IL-2 administration (9-grade 2, 3-grade 3, 1-grade 4). Eight of nine evaluable patients demonstrated immunologic reactions by increased IFN-gamma expressing T cells. One patient developed partial response at 12 weeks after the first vaccine. Nine months later, this patient achieved a complete response. In addition, two patients had stable disease for 9 and 4 months, respectively; one patient had a mixed response. Our findings demonstrated that dendritoma vaccines with a low dose of IL-2 can be safely administered to patients with metastatic melanoma and induce immunological and clinical responses.
开展了一项针对转移性黑色素瘤患者的试点临床试验，使用树突状瘤（由树突状细胞与肿瘤细胞融合而成的纯化杂交细胞，并结合低剂量白细胞介素-2），以确定其安全性以及潜在的免疫和临床反应。10名转移性黑色素瘤患者被纳入该研究。树突状瘤疫苗是通过将用绿色荧光染料染色的树突状细胞与用红色荧光染料染色的经辐照的自体肿瘤细胞融合，并使用直接荧光激活细胞分选法纯化杂交细胞而制备的。初始疫苗通过皮下注射给药，随后给予白细胞介素-2，剂量从300万单位/平方米至900万单位/平方米，连续5天递增。在不使用白细胞介素-2的情况下，每隔3个月重复接种疫苗，最多接种5次。通过表达干扰素-γ（IFN-γ）的T细胞增加来测量免疫反应。疫苗剂量范围为250,000至1,000,000个树突状瘤。没有直接归因于疫苗的2级或更高毒性。所有患者均因白细胞介素-2给药出现毒性反应（9例2级，3例3级，1例4级）。9名可评估患者中有8名通过表达IFN-γ的T细胞增加表现出免疫反应。1例患者在首次接种疫苗后12周出现部分缓解。9个月后，该患者实现完全缓解。此外，2例患者分别有9个月和4个月的病情稳定；1例患者有混合反应。我们的研究结果表明，低剂量白细胞介素-2的树突状瘤疫苗可安全地用于转移性黑色素瘤患者，并诱导免疫和临床反应。
