Serial monoclonal antibody administration demonstrates therapeutic effects via induction of apoptosis in HPV related cervical cancer

Abstract Introduction All cervical cancer is caused by the persistent expression of human papillomavirus (HPV) E6 and E7 oncoproteins that interfere with p53 and Rb pathways, respectively. Virally specific treatments form an excellent basis for highly specific, low toxicity therapies. Methods Serial doses of anti-HPV 16/18 E6 C1P5 (Abcam) were compared against Cisplatin in the treatment of human cervical cancer derived tumors (CaSki). C1P5 and Cisplatin were administered on days 1, 4, and 7 after CaSki tumor size reached 3–5mm on the flank of athymic nude mice. Measurements were performed every 3 days during the 40 day observation period. After which the tumors were procured, paraffin embedded, and stained with H&E. SiHa cells which compare to HPV copies in patient explants (previously published) were used in mechanistic studies. Dual staining flow cytometry with PI and Annexin was performed to evaluate cell death and MTT assay was used to confirm findings. Results Tumor growth was inhibited in all treatment groups compared to untreated controls (p <0.05). No statistically significant differences between C1P5 treatment groups were noted when compared to cisplatin. However, on H&E we noted increased necrosis proportional to the number of doses: 1 dose 30%, 2 doses 60%, and 3 doses 85%. Dual-staining of Annexin and PI on flow cytometry demonstrated increased apoptosis as a result of C1P5 administration suggesting this as the underlying mechanism of increased necrosis. These results were corroborated by MTT assay (p<0.05). Conclusion Virally specific therapy is promising for the treatment of women with cervical cancer. To extend the paucity of options, further mechanistic understanding must be developed to derive maximal therapeutic benefit.