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Immunotherapy for prevention of postoperative recurrence in pancreatic cancer using cell therapy and vaccine therapy

使用细胞疗法和疫苗疗法预防胰腺癌术后复发的免疫疗法

基本信息

批准号：
15390397
负责人：
OKA Masaaki
金额：
$ 9.28万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

(1)Thirty patients with pancreatic cancer were treated by immunotherapy using MUC1-CTL after curative resection. Only 3 patient (10%) had liver recurrence. However, 19 patients (63%) had local recurrence. One year, 2 year, and 3 year survival rate were 83.3%, 32.4%, and 19.9%, respectively. This immunotherapy may prevent liver metastasis after surgery, but can not control local recurrence.(2)To evaluate safety and immunological responses, we conducted a phase I study of personalized peptide vaccination for pancreatic cancer patients (n=11). Namely, pre-vaccination peripheral blood mononuclear cells were screened for their reactivity in vitro to each of 14 or 16 peptides in HLA-A24(+) or -A2(+) patients, and only the reactive peptides (maximum:4) were vaccinated in vivo. This regimen was generally well tolerated, although inflammatory reactions at the injection site were observed in 7 patients. Delayed-type hypersensitivity to peptides used for vaccination was observed in 7 patients. Increased cellular and humoral immune responses to at least one of peptides used for vaccination were observed in the post-vaccination PBMCs and sera from 4 of 8 patients and 4 of 10 patients tested, respectively. The 6- and 12-month survival rates for patients who received >3 vaccinations (n=10) were 80% and 20%, respectively. Due to tolerability and capability of inducing specific immunity, further development of personalized peptide-based immunotherapy for pancreatic cancer patients is warranted.(3)We performed MUC1-CTL+personalized peptide-based immunotherapy in 3 patients undergone curative resection for pancreatic cancer. All patients still alive without recurrence.(4)Fifteen patients with unresectable or recurrence pancreatic cancer were treated with MUC1-CTL+MUC1 peptide stimulated dendritic cells (DC) therapy. One patients had CR and 4 patients had SD. No severe side effects was observed.

(1)30例胰腺癌患者在根治性切除术后接受MUC1-CTL免疫治疗。只有 3 名患者（10%）出现肝脏复发。然而，19 名患者（63%）出现局部复发。 1年、2年、3年生存率分别为83.3%、32.4%、19.9%。这种免疫疗法可以预防术后肝转移，但不能控制局部复发。(2)为了评估安全性和免疫学反应，我们对胰腺癌患者(n=11)进行了个性化肽疫苗接种的I期研究。即，在体外筛选接种前的外周血单核细胞对HLA-A24(+)或-A2(+)患者的14或16种肽中的每一种的反应性，并且仅对具有反应性的肽(最多：4种)进行体内疫苗接种。尽管在 7 名患者中观察到注射部位的炎症反应，但该方案总体耐受性良好。在 7 名患者中观察到对用于疫苗接种的肽出现迟发型超敏反应。在所测试的 8 名患者中的 4 名和 10 名患者中的 4 名的疫苗接种后 PBMC 和血清中，分别观察到对至少一种用于疫苗接种的肽的细胞和体液免疫应答增加。接受超过 3 次疫苗接种的患者 (n=10) 的 6 个月和 12 个月生存率分别为 80% 和 20%。由于耐受性和诱导特异性免疫的能力，有必要进一步开发针对胰腺癌患者的个性化肽免疫治疗。(3)我们对3名接受胰腺癌根治性切除的患者进行了MUC1-CTL+个性化肽免疫治疗。所有患者均存活，无复发。(4)15例不可切除或复发的胰腺癌患者接受MUC1-CTL+MUC1肽刺激的树突状细胞(DC)治疗。 1 名患者获得 CR，4 名患者获得 SD。没有观察到严重的副作用。