Clinical studies suggest that responses to HPV16 E6E7L2 fusion
protein (TA-CIN) vaccination alone are modest, and
GPI-0100 is a well-tolerated, potent adjuvant. Here we sought to optimize both the immunogenicity of TA-CIN via formulation with
GPI-0100 and treatment of HPV16+
cancer by vaccination after
cisplatin chemotherapy. HPV16 neutralizing serum antibody titers, CD4+ T cell proliferative and E6/E7-specific CD8+ T cell responses were significantly enhanced when mice were vaccinated subcutaneously (s.c.) or intramuscularly (i.m.) with TA-CIN formulated with
GPI-0100. Vaccination was tested for
therapy of mice bearing syngeneic HPV16 E6/E7+
tumors (TC-1) either in the lung or subcutaneously. Mice treated with TA-CIN/GPI-0100 vaccination exhibited robust E7-specific CD8+ T cell responses, which were associated with reduced
tumor burden in the lung, whereas mice receiving either component alone were similar to controls. Since vaccination alone was not sufficient for cure, mice bearing s.c. TC-1
tumor were first treated with two doses of
cisplatin and then vaccinated. Vaccination with TA-CIN/GPI-0100 i.m. substantially retarded
tumor growth and extended survival after
cisplatin therapy. Injection of TA-CIN alone, but not
GPI-0100, into the
tumor (i.t.) was similarly efficacious after
cisplatin therapy, but the mice eventually succumbed. However,
tumor regression and extended remission was observed in 80% of the mice treated with
cisplatin and then intra-tumoral TA-CIN/GPI-0100 vaccination. These mice also exhibited robust E7-specific CD8+ T cell and HPV16
neutralizing antibody responses. Thus formulation of TA-CIN with
GPI-0100 and intra-tumoral delivery after
cisplatin treatment elicits potent therapeutic responses in a murine model of HPV16+
cancer.