Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan: Clinical and immunological findings
Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan: Clinical and immunological findings
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DOI：
10.1016/j.ymthe.2004.07.001
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发表时间：
2004-10-01
影响因子：
12.4
通讯作者：
Asano, S
中科院分区：
文献类型：
--
作者：
Tani, K;Azuma, M;Asano, S
“我们从6名患有IV期肾细胞癌（RCC）的日本患者中生产了经致死性辐照的逆转录病毒GM-CSF转导的自体肾肿瘤细胞疫苗（GVAX）。4名患者接受了6-17次GVAX，范围为1.4 x 10（8）至3.7 x 10（8）个细胞。在总共48次疫苗接种中，没有发生严重的不良事件。疫苗接种后，所有患者的DTH皮肤试验均呈自体RCC（auto-RCC）阳性。接种部位显示CD 4（+）T细胞、嗜酸性粒细胞和HLA-DR阳性细胞的显著浸润。使用外周血淋巴细胞的细胞免疫反应的动力学分析显示，增强对自身肾细胞癌的增殖反应在4例患者中，和对自身肾细胞癌的细胞毒性增强在3例患者中。T细胞受体β链分析显示外周血、DTH部位皮肤活检标本和肿瘤中T细胞的寡克隆扩增。Western印迹分析表明诱导了针对自身RCC的体液免疫应答。四名患者中有两名在首次接种低剂量白细胞介素-2疫苗后分别存活了58个月和40个月。我们的研究结果表明，GVAX大大增强了抗肿瘤细胞和体液免疫反应，这可能有助于我们的患者在本研究中相对较长的生存时间。
`We produced lethally irradiated retrovirally GM-CSF-transduced autologous renal tumor cell vaccines (GVAX) from six Japanese patients with stage IV renal cell cancer (RCC). Four patients received GVAX ranging from 1.4 x 10(8) to 3.7 x 10(8) cells on 6-17 occasions. Throughout a total of 48 vaccinations, there were no severe adverse events. After vaccination, DTH skin tests became positive to autologous RCC (auto-RCC) in all patients. The vaccination sites showed significant infiltration by CD4(+) T cells, eosinophils, and HLA-DR-positive cells. The kinetic analyses of cellular immune responses using peripheral blood lymphocytes revealed an enhanced proliferative response against auto-RCC in four patients, and cytotoxicity against auto-RCC was augmented in three patients. T cell receptor beta-chain analysis revealed oligoclonal expansion of T cells in the peripheral blood, skin biopsy specimens from DTH sites, and tumors. Western blot analysis demonstrated the induction of a humoral immune response against auto-RCC. Two of the four patients are currently alive 58 and 40 months after the initial vaccination with low-dose interleukin-2. Our results suggest that GVAX substantially enhanced the antitumor cellular and humoral immune responses, which might have contributed to the relatively long survival times of our patients in the present study.