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

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


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.

Keywords: Cyclophosphamide; Pancreatic cancer; Th17 cells; Tumor lysates; mHSP65.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / administration & dosage*
  • Bacterial Proteins / administration & dosage*
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Chaperonin 60 / administration & dosage*
  • Complex Mixtures / administration & dosage
  • Cyclophosphamide / administration & dosage*
  • Drug Synergism
  • Female
  • Humans
  • Immunotherapy / methods*
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / therapy*
  • Up-Regulation / drug effects


  • Antigens, Neoplasm
  • Bacterial Proteins
  • Cancer Vaccines
  • Chaperonin 60
  • Complex Mixtures
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • heat-shock protein 65, Mycobacterium
  • Cyclophosphamide