Immune stimulation for the treatment of papilloma. Ann Otol Rhinol Laryngol 2005 Sep;114(9):657-61
Date
10/26/2005Pubmed ID
16240926DOI
10.1177/000348940511400901Scopus ID
2-s2.0-25144468335 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
OBJECTIVES: There is no curative therapy for recurrent respiratory papillomatosis. Unmethylated dinucleotides of cytosine and guanine (CpG) are potent immune stimulants that have shown efficacy against tumors as monotherapy, as vaccine adjuvants, and in combination with chemotherapies. We examined the therapeutic effect of CpG oligodeoxynucleotides in the treatment of papillomavirus in a cottontail rabbit model (CRPV).
METHODS: Twenty rabbits were infected with CRPV; 10 were treated with 11 weekly CpG inoculations while treatment control rabbits received intralesional saline solution. Eight rabbits (4 treatment, 4 control) were rechallenged with CRPV 17 weeks after the initial viral challenge and monitored for new papilloma development.
RESULTS: Papillomas developed in all 20 rabbits (100%) within 4 weeks of infection. The diagnosis was confirmed histologically. There was no difference in the average tumor burden between the treatment and control groups after 11 weeks of CpG treatments or after 9 additional weeks of observation. There was no difference between the groups in papilloma size at the site of the injections, nor was there eradication of papillomas at remote sites in either group. No new papillomas developed in any of the 8 animals that were rechallenged.
CONCLUSIONS: We have reproduced an effective mammalian papilloma model for preclinical immunotherapeutic testing. Despite the potency of CpG in triggering host immunity, CpG oligodeoxynucleotide did not show a therapeutic effect against the large papilloma burdens tested in this study. The lack of effect suggests that either enhanced papilloma antigen presentation or targeting of immune-evasive mechanisms used by the papillomas is needed to treat bulky disease with an immunotherapeutic strategy.
Author List
Poetker DM, Kerschner JE, Patel NJ, Bauman NM, Sandler ADAuthor
David M. Poetker MD Chief, Professor in the Otolaryngology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adjuvants, ImmunologicAnimals
Cottontail rabbit papillomavirus
CpG Islands
Disease Models, Animal
Injections, Intralesional
Laryngeal Neoplasms
Papilloma
Papillomavirus Infections
Rabbits
Random Allocation
Treatment Failure