Cellular Vaccines Modified with Hyper IL6 or Hyper IL11 Combined with Docetaxel in an Orthotopic Prostate Cancer Model

Anticancer Res. 2015 Jun;35(6):3275-88.

Abstract

Background: Whole-cell-based vaccines modified with Hyper-IL-6 (H6) and Hyper-IL-11 (H11) have demonstrated high activity in murine melanoma and renal cancer models.

Materials and methods: H6 and H11 cDNA was transduced into TRAMP cells (TRAMP-H6 and TRAMP-H11). An orthotopic TRAMP model was employed. The efficacy of TRAMP-H6 and TRAMP-H11 in combination with docetaxel was evaluated. Immune cells infiltrating tumors were assessed.

Results: Immunization with TRAMP-H6 and TRAMP-H11 vaccines extended OS of mice. Addition of docetaxel to TRAMP-H6 and TRAMP-H11 vaccines further extended OS of the animals. Vaccination with TRAMP-H6 alone and TRAMP-H11 combined with docetaxel augmented tumor infiltration by activated CD8(+) and CD4(+) T-cells and attracted higher number of activated, mature DCs infiltrating tumors. Addition of docetaxel to TRAMP-H6, TRAMP-H11, TRAMP-Adv700 vaccines enhanced the infiltration of the tumor by NK cells.

Conclusion: Addition of docetaxel to modified TRAMP vaccines improved clinical benefit of treated mice and enhanced anti-tumor immune response.

Keywords: Cancer vaccine; docetaxel; immunotherapy; murine model; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Disease Models, Animal
  • Docetaxel
  • Humans
  • Immunotherapy*
  • Interleukin-11 / administration & dosage
  • Interleukin-11 / genetics*
  • Interleukin-6 / administration & dosage
  • Interleukin-6 / genetics*
  • Killer Cells, Natural / immunology
  • Male
  • Mice
  • Neoplastic Stem Cells / immunology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology
  • Recombinant Fusion Proteins / immunology
  • Taxoids / administration & dosage

Substances

  • Cancer Vaccines
  • IL11 protein, human
  • IL6 protein, human
  • Interleukin-11
  • Interleukin-6
  • Recombinant Fusion Proteins
  • Taxoids
  • Docetaxel