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）治疗切除术后使用MUC1-CTL通过免疫疗法治疗30例胰腺癌患者。只有3名患者（10％）患有肝复发。但是，19例患者（63％）有局部复发。一年，2年和3年的生存率分别为83.3％，32.4％和19.9％。这种免疫疗法可以预防手术后的肝转移，但不能控制局部复发。（2）为了评估安全性和免疫反应，我们对胰腺癌患者的个性化肽疫苗接种进行了I期研究（n = 11）。也就是说，在HLA-A24（+）或-a2（+）患者中，在体外筛选了疫苗接种前血液单核细胞的反应性，并且仅在VIVO中疫苗接种反应性肽（最大值：4）。尽管在7例患者中观察到了注射部位的炎症反应，但该方案通常耐受性良好。在7例患者中观察到对用于疫苗接种的肽的延迟型超敏反应。在疫苗接种后PBMC中观察到了至少一种用于疫苗接种的肽的细胞和体液免疫反应增加，分别从8例患者中的4例和10名患者中的4例观察到了血清。接受> 3次疫苗接种（n = 10）的患者的6个月和12个月的存活率分别为80％和20％。由于诱导特定免疫力的耐受性和能力，必须进一步开发基于个性化肽的胰腺癌患者的免疫疗法。（3）我们在3例患者中对3例患者进行了MUC1-CTL+基于个性化肽的免疫疗法，用于治疗胰腺癌。所有仍然没有复发的患者。（4）用MUC1-CTL+MUC1肽刺激的树突状细胞（DC）治疗15例无法切除或复发胰腺癌患者。一名患者患有CR，有4例患者患有SD。未观察到严重的副作用。