Antigen-specific immunotherapy for human papillomavirus 16 E7-expressing tumors grown in the liver.
OBJECTIVE
We have previously reported a recombinant vaccinia-based vaccine (vac-Sig/E7/LAMP-1) that demonstrated a significant anti-tumor effect in a subcutaneous tumor challenge model. Since the liver is one of the most common sites for tumor metastasis and organ microenvironments may modulate tumor cell responses to therapies, the aim of the present study was to evaluate the potency of vac-Sig/E7/LAMP-1 in treating E7-expressing tumors grown in the liver.


METHODS
For in vivo tumor prevention experiments, mice were vaccinated intraperitoneally with vac-Sig/E7/LAMP-1 followed by intrahepatic tumor challenge. For in vivo tumor regression experiments, mice were first challenged with tumor cells and then vaccinated with vac-Sig/E7/LAMP-1 intraperitoneally. In addition, enzyme-linked immunospot assays were used to determine the frequency of E7-specific T cell precursors.


RESULTS
For in vivo tumor protection experiments, tumor growth was observed in all of the mice vaccinated with wild-type vaccinia and 60% of the mice vaccinated with wild-type E7 vaccinia. All of the mice vaccinated with vac-Sig/E7/LAMP-1 remained tumor-free 30 days after tumor challenge. For the tumor regression assays, all of the mice vaccinated with vac-Sig/E7/LAMP-1 remained tumor-free 30 days after vaccination. In contrast, all of those mice receiving culture medium, wild-type vaccinia, or wild-type E7 vaccinia developed tumors in the liver. In addition, mice vaccinated with vac-Sig/E7/LAMP-1 had the highest E7-specific CD8+ T cell precursors.


CONCLUSIONS
Our data suggest that vac-Sig/E7/LAMP-1 is an effective vaccine for controlling E7-expressing tumors grown in the liver and our model suggests that antigen-specific immunotherapy may represent a powerful tool for treating liver tumors with characterized tumor-specific antigens. In addition, our data indicate that the number of E7-specific CD8+ T cell precursors directly correlated with the anti-tumor effect generated by Sig/E7/LAMP-1 vaccinia.
Chen
C H
CH
Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Suh
K W
KW
Ji
H
H
Choti
M A
MA
Pardoll
D M
DM
Wu
T C
TC
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology; D002455:Cell Division; D000939:Epitopes; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000032:analysis* / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D015703:Antigens, CD; D000939:Epitopes; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16