Combination therapy with immunotherapy and chemotherapy for pancreatic cancer

免疫疗法和化疗联合治疗胰腺癌

• 批准号: 14571200
• 负责人: YAMAMOTO Koutaro
• 金额: $ 2.3万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571200/
• 关键词: Pancreatic cancer; Immunotherapy; Chemotherapy

On this project, we attempted to find clinically effective therapy against pancreatic cancer using the combination with immunotherapy and chemotherapy. For immunotherapy, we conducted two phase I trials of MUC1 peptide vaccination and personalized peptide vaccination. MUC1 mucin is glycoprotein, which is strongly recognized on the surface of pancreatic cancer cells and induces MUC1-specific cytotoxic T lymphocytes without restriction of HLA. We vaccinated 9 patients with 300, 1000, or 3000 mg of the 105 amino acid MUC1 peptide. The MUC1 vaccination was well tolerated in all patients and did not produce any side effects. In l out of 9 patients tumor markers decreased, but in the others their diseases showed progression. Secondary we applied another phase I study with personalized peptide vaccination to 10 patients with pancreatic cancer. Namely, pre-vaccinated peripheral blood mononuclear cells were screened for the reactivity in vitro to each of 14 or 16 peptide candidates in HLA-A24^+ … More or -A2^+ patients, and then only the reactive peptides were vaccinated in vivo. This regimen was generally well tolerated without hematological toxicity, although inflammatory reactions at the injection site were observed in ? patients. Moreover fever, anorexia, and fatigue were observed -in 3, 1, and 1 patient, respectively. Of 10 patients who received more than 3 vaccinations and were eligible for clinical evaluation, 3 showed stable disease and 7 demonstrated progressive disease at the time of the 6th vaccination. One patient of 3 with stable disease has been alive for 30 months after the initial treatment. We demonstrated feasibility and safety of two vaccination immunotherapy, however, these therapy did not show a obvious survival benefit : On the other hand, we established a new human pancreatic cancer cell line, designated YPK-1. 50% inhibitory concentration (IC50) to YPK-1 of gemcitabine (GEM) was 0.0063 ug/ml. IC50 of cisplatin and 5-fluorouracil were 1.26 and 3.16 ug/ml, respectively. These data showed GEM may be clinically effective for pancreatic cancer among chemotherapeutic agents. In conclusion, further development of combination with personalized peptide based immunotherapy and chemotherapy using GEM for pancreatic cancer is warranted Less

在这个项目中，我们试图找到临床上有效的治疗胰腺癌的联合免疫治疗和化疗。对于免疫疗法，我们进行了MUC 1肽疫苗接种和个性化肽疫苗接种的两项I期试验。MUC 1粘蛋白是一种糖蛋白，它在胰腺癌细胞表面被强烈识别，并诱导MUC 1特异性细胞毒性T淋巴细胞，而不受HLA的限制。我们用300、1000或3000 mg的105个氨基酸的MUC 1肽对9名患者进行了疫苗接种。MUC 1疫苗接种在所有患者中耐受性良好，没有产生任何副作用。9例患者中1例肿瘤标志物下降，但其他患者的疾病显示进展。其次，我们对10名胰腺癌患者进行了另一项I期研究，采用个性化肽疫苗接种。也就是说，筛选预先接种的外周血单核细胞对HLA-A24^+中14或16种候选肽的体外反应性。 ...更多信息 或-A2^+患者，然后仅在体内接种反应性肽。该方案一般耐受良好，无血液学毒性，虽然在注射部位的炎症反应观察？患者此外，分别在3例、1例和1例患者中观察到发热、厌食和疲乏。在接受3次以上疫苗接种并有资格进行临床评价的10名患者中，3名患者在第6次疫苗接种时显示疾病稳定，7名患者在第6次疫苗接种时显示疾病进展。3例病情稳定的患者中有1例在初始治疗后存活了30个月。我们证明了两种疫苗免疫疗法的可行性和安全性，然而，这些疗法没有显示出明显的生存益处：另一方面，我们建立了一种新的人胰腺癌细胞系，命名为YPK-1。吉西他滨（GEM）对YPK-1的半数抑制浓度（IC_（50））为0.0063 μ g/ml。顺铂和5-氟尿嘧啶的IC_（50）分别为1.26和3.16 μ g/ml。这些数据表明，吉西他滨可能是临床有效的胰腺癌化疗药物。总之，有必要进一步开发基于个性化肽的免疫疗法和使用GEM的化疗组合用于胰腺癌。

项目成果

Koutaro Yamamoto: "Establishment and Characterization of a new pancreatic cancer cell line, YPK-1."The Bullitin of the Yamaguchi Medical School. 49(1-2). 33-42 (2002)

Koutaro Yamamoto：“新胰腺癌细胞系 YPK-1 的建立和表征。”山口医学院公告。

Koutaro Yamamoto: "Establishment and Characterization of a new pancreatic cancer cell line, YPK-1"The Bullion of the Yamaguchi Medical School. 49(1-2). 33-42 (2002)

Koutaro Yamamoto：“新胰腺癌细胞系 YPK-1 的建立和表征”山口医学院金币。