Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: A phase I trial of safety and immune activation
Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: A phase I trial of safety and immune activation
复制标题
DOI：
10.1200/jco.2001.19.1.145
复制
发表时间：
2001-01-01
影响因子：
45.3
通讯作者：
Yeo, CJ
中科院分区：
文献类型：
--
作者：
Jaffee, EM;Hruban, RH;Yeo, CJ
目的：分泌异基因粒细胞-巨噬细胞集落刺激因子（GM-CSF）的肿瘤疫苗可以治愈小鼠中已建立的肿瘤，但其对人类肿瘤的疗效尚不确定。我们已经开发了一种新的分泌OM-CSF的胰腺肿瘤疫苗。为了确定其安全性和诱导抗肿瘤免疫反应的能力，我们进行了一项I期临床试验，手术切除的腺癌pancreas.Patients和方法：14例患者与阶段1，2，或3胰腺癌。胰腺切除术后8周，3名患者接受1 × 10（7）疫苗细胞，3名患者接受5 × 10（7）疫苗细胞，3名患者接受10 × 10（7）疫苗细胞，5名患者接受50 × 10（7）疫苗细胞。14名患者中有12名接受了为期6个月的辅助放疗和化疗。一个月后完成辅助治疗，6例仍在缓解接受了多达三个额外的每月接种相同的疫苗剂量，他们已经收到original.Results：没有剂量限制性毒性反应。在接受大于或等于10 × 10（7）个疫苗细胞的三名患者中，疫苗接种诱导了对自体肿瘤细胞的迟发型超敏反应（DTH）增加。这三个病人似乎也有增加的无病生存时间，剩余的无病至少25个月后diagnosed.Conclusion：同种异体GM-CSF分泌肿瘤疫苗是安全的胰腺癌患者。这种疫苗的方法似乎诱导剂量依赖性的全身抗肿瘤免疫，如通过增加接种后DTH反应对自体肿瘤。这种方法在胰腺癌患者中的进一步临床评价是必要的。J Clin Oncol 19：145-156. (C)2001年，美国临床肿瘤学会。
Purpose: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel OM-CSF-secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas.Patients and Methods: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 x 10(7) vaccine cells, three patients received 5 x 10(7) vaccine cells, three patients received 10 x 10(7) vaccine cells, and five patients received 50 x 10(7) vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally.Results: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received greater than or equal to 10 x 10(7) vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis.Conclusion: Allogeneic GM-CSF-secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous rumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted. J Clin Oncol 19:145-156. (C) 2001 by American Society of Clinical Oncology.