Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein

Int J Cancer. 1998 Sep 25;78(1):41-5. doi: 10.1002/(sici)1097-0215(19980925)78:1<41::aid-ijc8>3.0.co;2-x.

Abstract

An important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported a recombinant vaccinia-based vaccine (Sig/E7/LAMP-1) that demonstrated significant anti-tumor effect in a subcutaneous tumor challenge model. In this study, we investigated the potency of the Sig/E7/ LAMP-1 vaccine in preventing and treating metastatic tumors. A tumor metastasis model was generated by injecting human papillomavirus type 16 (HPV-16) E6/E7 expressing tumor cells, designated TC-1, into the tail vein of syngeneic C57BL/6 mice. All the naive mice injected with 1 x 10(6) TC-1 cells developed tumors confined exclusively to the lungs within 1 month. For in vivo tumor prevention experiments, mice were vaccinated with Sig/E7/ LAMP-1 followed by tumor challenge. While tumor growth was observed in all of the mice (10/10) in the control groups, 8 of 10 vaccinated mice (80%) remained tumor-free 2 months post-tumor challenge. For in vivo treatment experiments, mice were first inoculated with TC-1 cells and then vaccinated with Sig/E7/ LAMP-1. Treatment with Sig/E7/LAMP-1 was effective in eliminating preexisting tumor cells in 4 of 5 vaccinated mice. Most importantly, treatment with Sig/E7/LAMP-1 resulted in regression of fully established lung tumors in 10% (5/10) of vaccinated mice. Our data suggest that the Sig/E7/LAMP-1 vaccine is effective in controlling the hematogenous spread of TC-1 tumor cells. In addition, the TC-1 lung metastasis model can be used to test the efficacy of various E6/E7-specific vaccines and immunotherapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / therapeutic use*
  • Cancer Vaccines / therapeutic use*
  • Female
  • Genetic Vectors
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy*
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Glycoproteins / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Vaccinia virus

Substances

  • Antigens, CD
  • Cancer Vaccines
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Glycoproteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • oncogene protein E7, Human papillomavirus type 16