A Murine Model for the Effects of Pelvic Radiation and Cisplatin Chemotherapy on Human Papillomavirus Vaccine Efficacy

• Published in: Clinical cancer research 2001-03, Vol.7 (3), p.876s-881s
• Main Authors: SMALL, Laurie A, DA SILVA, Diane M, DE VISSER, Karin E, VELDERS, Markwin P, FISHER, Susan G, POTKUL, Ronald K, KAST, W. Martin
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cancer Vaccines; Cisplatin - adverse effects; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Immunotherapy; Medical sciences; Mice; Mice, Inbred C57BL; Neoplasms - prevention & control; Oncogene Proteins, Viral - chemistry; Oncogene Proteins, Viral - immunology; Papillomaviridae - metabolism; Papillomavirus E7 Proteins; Papillomavirus Vaccines; Peptides - chemistry; Peptides - metabolism; Pharmacology. Drug treatments; Radiation-Sensitizing Agents - pharmacology; Radiotherapy - adverse effects; Time Factors
• ISSN: 1078-0432; 1557-3265

Therapeutic human papillomavirus (HPV) vaccines for cervical cancer depend on a competent immune system to be effective. However, cancer patients are often found to be immunosuppressed, which could be attributable to prior radiation, chemotherapy, or the tumor burden itself. This study investigated whether pelvic radiation or cisplatin treatment affected the efficacy of an HPV vaccine and how long these effects lasted. Mice were given pelvic radiation, 2 Gy/day to a total dose of 45 Gy, or 5 mg/kg/week of cisplatin for 3 weeks. Mice were then immunized with an HPV-16 peptide vaccine between 0 and 16 weeks after their treatment. An ELISPOT analysis revealed that a reduced level of peptide-specific, IFN γ -producing spleen cells was present in immunized mice treated previously with pelvic radiation or cisplatin compared with immunized mice that had not been treated. However, when mice were challenged with HPV-16-expressing tumor cells, immunized mice developed no tumors, regardless of prior treatment, whereas nonimmunized mice did develop tumors. Our results suggest that pretreatment with pelvic radiation or cisplatin alone does not prevent the induction of an effective immune response by a peptide vaccine. These data will have important implications for immunotherapeutic treatment of pretreated cancer patients, especially in the adjuvant setting when immunosuppression by tumor burden would be low.