Immunotherapy for Lewis lung carcinoma utilizing dendritic cells infected with CK19 gene recombinant adenoviral vectors

Oncol Rep. 2015 Nov;34(5):2289-95. doi: 10.3892/or.2015.4231. Epub 2015 Aug 27.

Abstract

Dendritic cells (DCs) as 'professional' antigen-presenting cells (APCs) initiate and regulate immune responses to various antigens. DC-based vaccines have become a promising modality in cancer immunotherapy. Cytokeratin 19 (CK19) protein is expressed at high levels in lung cancer and many other tumor cells, suggesting CK19 as a potential tumor‑specific target for cancer immune therapy. We constructed a recombinant adenoviral vector containing the CK19 gene (rAd-CK19). DCs transfected with rAd-CK19 were used to vaccinate C57BL/6 mice bearing xenografts derived from Lewis lung carcinoma (LLC) cells. The transfected DCs gave rise to potent CK19-specific cytotoxic T lymphocytes (CTLs) capable of lysing LLC cells. Mice immunized with the rAd‑CK19-DCs exhibited significantly attenuated tumor growth (including tumor volume and weight) when compared to the tumor growth of mice immunized with rAd-c DCs or DCs during the 24-day observation period (P<0.05). The results revealed that the mice vaccinated with the rAd-CK19-DCs exhibited a potent protective and therapeutic antitumor immunity to LLC cells in the subcutaneous model along with an inhibitive effect on tumor growth compared to the mice vaccinated with the rAd-c DCs or DCs alone. The present study proposes a meaningful mode of action utilizing rAd-CK19 DCs in lung cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antibody-Dependent Cell Cytotoxicity
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / therapy*
  • Cell Line, Tumor
  • Cell Proliferation
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Gene Expression
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Keratin-19 / biosynthesis
  • Keratin-19 / genetics
  • Keratin-19 / immunology*
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • T-Lymphocytes, Cytotoxic / immunology
  • Transduction, Genetic

Substances

  • Cancer Vaccines
  • Keratin-19