低剂量环磷酰胺给药增强荷胰腺癌小鼠体内mHSP65-TTL的抗肿瘤活性。

Antitumor activity of mHSP65-TTL enhanced by administration of low dose cyclophosphamide in pancreatic cancer-bearing mice.

作者信息

Xuan Wei, Yan Youyou, Wan Min, Wu Xiuli, Ji Degang, Wang Liying, Lin Chao, Chen Yang, Yu Yongli, Zhang Xuewen

机构信息

Department of Hepatobiliary-Pancreatic Surgery, Third Hospital (China-Japan Union Hospital) of Jilin University, Changchun 130021, China.

Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.

出版信息

Int Immunopharmacol. 2015 Jul;27(1):95-103. doi: 10.1016/j.intimp.2015.04.014. Epub 2015 Apr 20.

DOI:10.1016/j.intimp.2015.04.014

PMID:25907246

Abstract

Pancreatic cancer remains a lethal malignancy. Despite chemotherapy or/and radiotherapy after the surgery, the improvement on the overall survival of the patients has still been minimal. To develop novel therapeutic approaches, we tried to prepare mHSP65-TTL, a candidate vaccine prepared by mixing the recombinant mycobacterial heat shock protein 65 (mHSP65) with tumor tissue lysate (TTL) of Panc02 pancreatic cancer tissue. The mHSP65-TTL were used to immune the C57BL/6 mice implanted with the Panc02 cancer cells, in combination with or without low dose cyclophosphamide (CY). The results showed that mHSP65-TTL significantly prolonged the survival of the pancreatic cancer bearing mice and low dose CY enhanced the efficacy of the mHSP65-TTL. In addition, we detected mRNA expression of RORγt and IL-17A in spleen cells of mice received mHSP65-TTL or mHSP65-TTL plus CY, and found that mHSP65-TTL up-regulated mRNA expressions of RORγt and IL-17A, CY alone or mHSP65-TTL plus CY up-regulated mRNA expressions of RORγt. The work could provide an insight into a combinational approach for the immunotherapy of pancreatic cancer.

摘要

胰腺癌仍然是一种致命的恶性肿瘤。尽管在手术后进行了化疗或/和放疗，但患者总体生存率的改善仍然微乎其微。为了开发新的治疗方法，我们尝试制备mHSP65-TTL，这是一种通过将重组分枝杆菌热休克蛋白65（mHSP65）与Panc02胰腺癌组织的肿瘤组织裂解物（TTL）混合制备的候选疫苗。mHSP65-TTL用于免疫接种了Panc02癌细胞的C57BL/6小鼠，联合或不联合低剂量环磷酰胺（CY）。结果表明，mHSP65-TTL显著延长了荷胰腺癌小鼠的生存期，低剂量CY增强了mHSP65-TTL的疗效。此外，我们检测了接受mHSP65-TTL或mHSP65-TTL加CY的小鼠脾细胞中RORγt和IL-17A的mRNA表达，发现mHSP65-TTL上调了RORγt和IL-17A的mRNA表达，单独使用CY或mHSP65-TTL加CY上调了RORγt的mRNA表达。这项工作可为胰腺癌免疫治疗的联合方法提供见解。