Antigen-specific immunotherapy for human papillomavirus 16 E7-expressing tumors grown in the liver

Background/Aims: We have previously reported a recombinant vaccinia-based v accine (vac-Sig/E7/LAMP-1) that demonstrated a significant anti-tumor effec t in a subcutaneous tumor challenge model, Since the liver is one of the mo st common sites for tumor metastasis and organ microenvironments may modula te tumor cell responses to therapies, the aim of the present study was to e valuate the potency of vac-Sig/E7/LAMP-1 in treating E7-expressing tumors g rown in the liver. Methods: For in vivo tumor prevention experiments, mice were vaccinated int raperitoneally with vac-Sig/E7/LAMP-1 followed by intrahepatic tumor challe nge. For in vivo tumor regression experiments, mice were first challenged w ith tumor cells and then vaccinated with vac-Sig/E7/LAMP-1 intraperitoneall y. 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 observe d 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 t umor regression assays, all of the mice vaccinated with vac-Sig/E7/LAMP-1 r emained tumor-free 30 days after vaccination. In contrast, all of those mic e receiving culture medium, wild-type vaccinia, or wild-type E7 vaccinia de veloped tumors in the liver. In addition, mice vaccinated with vac-Sig/E7/L AMP-1 had the highest E7-specific CD8(+) T cell precursors. Conclusions: Oar data suggest that vac-Sig/E7/LAMP-1 is an effective vaccin e for controlling E7-expressing tumors grown in the liver and our model sug gests that antigen-specific immunotherapy may represent a powerful tool for treating liver tumors with characterized tumor-specific antigens, In addit ion, our data indicate that the number of E7-specific CD8(+) T cell precurs ors directly correlated with the anti-tumor effect generated by Sig/E7/LAMP -1 vaccinia.