Author:

Abstract:

Objectives: Previous results showed that intratumoral treatment with cidofovir (CDV) of a primary human papillomavirus (HPV+) xenograft temporally reduced the size of an untreated secondary HPV+ tumor. Here, we added adjuvant (aluminum-0.5% + MPLA-0.05%) to CDV treatment to prolong and/or enhance the effects on the secondary tumor. Methods: nu/nu NMRI mice were injected subcutaneously with SiHa cells (tumor 1, T1). T2 was induced after three weeks of intratumoral treatment of T1. Immune cells in spleen, lymph nodes (LN) and tumors were evaluated. Animals were subdivided into 6 groups: (A) no tumor; (B) only secondary tumor (T2); (C) T1 (PBS-adjuvant) and T2; (D) T1 (CDV-adjuvant) and T2; (E) T1 (CDV) and T2; (F) T1 (adjuvant) and T2. Results: CDV had a beneficial effect on T1, regardless of adjuvant addition. T2 grew slower in the CDV treated mice up till 2 weeks after its induction, compared to other groups. A slightly smaller T2 size was observed in group D (CDV+adjuvant) compared to group E (CDV). A higher percentage of γδ-T-cells and NK-cells in T2 of mice in group D compared to group E was observed. In the LN of groups injected with adjuvant, higher percentages of γδ-T-cells were observed. The percentage of γδ-T-cells, NK-cells and B-cells were higher in spleen and T1 of mice with smaller tumors than in mice with big tumors. Conclusion: This suggests that the indirect effect of CDV on an untreated secondary HPV positive tumor could be related to the stimulation of γδ-T-cells and NK-cells.