Intralesional interferon alpha-2b as a novel treatment for periocular squamous cell carcinoma in horses.
Abstract: To determine the safety and efficacy of perilesional human recombinant interferon alpha-2b (IFNα2b) for treatment of periocular squamous cell carcinoma (PSCC) in horses. Methods: Eleven horses (12 eyes) with PSCC were enrolled in this prospective clinical study with owner consent. Methods: Systemically healthy horses were included in the study following confirmation of PSCC via biopsy. Every two weeks for a maximum of six treatments, horses were sedated and perilesional injection of IFNα2b (10 million IU) was performed. Tumors were measured prior to each injection and at one, three, and 12 months after treatment completion. A greater than 50% reduction in tumor size was considered positive response to treatment (i.e., partial or complete response). Development of anti-IFNα2b antibodies was assessed using serum samples obtained after treatment initiation and compared with treatment responses. Antibody concentrations were analyzed using a mixed model. Statistical significance was considered p < 0.05. Results: Each horse received four to six perilesional injections of IFNα2b. Five of 12 eyes (4/11 horses) responded to treatment. Two of five eyes showed complete resolution of gross PSCC. No systemic adverse effects were seen. Local swelling occurred during treatment protocol in 6/11 horses but resolved without intervention. All horses developed serum anti-IFNα2b antibodies. There was no evidence of statistical difference in antibody concentration between responders and non-responders. Conclusions: Perilesional administration of IFNα2b was found to be well-tolerated in horses with PSCC, and induced tumor regression in 42% of treated eyes. Treatment failure appears unrelated to the development of IFNα2b antibodies.
Copyright: © 2024 Martabano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publication Date: 2024-02-21 PubMed ID: 38381740PubMed Central: PMC10881003DOI: 10.1371/journal.pone.0297366Google Scholar: Lookup
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Summary
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The study tests the use of perilesional human recombinant interferon alpha-2b (IFNα2b) as a novel treatment for cancer around the eye area (periocular squamous cell carcinoma or PSCC) in horses. The treatment showed positive results in around 42% of the treated horses with no severe side effects, suggesting that it may be a viable treatment option for PSCC in horses.
Study Methodology
- The research involved a clinical trial on 11 systematically healthy horses (with 12 affected eyes) diagnosed with PSCC, conducted with owner consent.
- The horses received injections of IFNα2b (10 million IU) around the lesion every two weeks, for a maximum of six treatments.
- The size of the tumors was measured before each injection and at one, three, and twelve months after the completion of treatment.
- The appearance of anti-IFNα2b antibodies was noted after initiation of the treatment, and compared with the treatment responses.
- A successful treatment response was defined as a reduction in tumor size by more than 50% (whether partial or complete).
- The experiment also included statistical analysis of the collected data, marking significance at p<0.05.
Results of the Study
- Each horse received between four to six injections of IFNα2b perilesionally.
- Of the 12 treated eyes, five responded positively to the treatment, with two eyes showing complete resolution of PSCC.
- The trial did not cause any systemic adverse effects.
- Around half of the horses (6/11) experienced local swelling during the treatment protocol, but this resolved without intervention.
- All horses developed serum anti-IFNα2b antibodies, although there was no significant statistical difference in antibody concentrations between responders and non-responders.
Conclusions
- The study concluded that the perilesional administration of IFNα2b was well-tolerated in horses with PSCC and led to tumor regression in 42% of treated eyes.
- The research suggested that the failure of the treatment did not relate to the formation of anti-IFNα2b antibodies.
- While the initial results are promising, further research is needed to develop the treatment and refine the methodology. The experiment could also be expanded to include a larger number of horses to ensure more statistically significant results.
Cite This Article
APA
Martabano BB, Dow S, Chow L, Williams MMV, Mack MK, Bellone R, Wotman KL.
(2024).
Intralesional interferon alpha-2b as a novel treatment for periocular squamous cell carcinoma in horses.
PLoS One, 19(2), e0297366.
https://doi.org/10.1371/journal.pone.0297366 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
- Veterinary Genetics Laboratory and Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
Conflict of Interest Statement
The authors have declared that no competing interests exist.
References
This article includes 26 references
- Montgomery KW. Equine ocular neoplasia: A review.. Equine Vet Edu 2014; 26: 372–80.
- Brooks DE, Matthews A, Clode AB. Disease of the cornea.. In: Gilger BC, editors. Equine Ophthalmology. 3rd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2017. 323–329.
- King TC, Priehs DR, Gum GG, Miller TR. Therapeutic management of ocular squamous cell carcinoma in the horse: 43 cases (1979–1989).. Equine Vet J 1991; 23: 449–52.
- Dugan SJ, Curtis CR, Roberts SM, Severin GA. Epidemiologic study of ocular/adnexal squamous cell carcinoma in horses.. J Am Vet Med Assoc 1991;198: 251–6.
- Lassaline M, Cranford TL, Latimer CA, Bellone RR. Limbal squamous cell carcinoma in Haflinger horses.. Vet Ophthalmol 2015;18: 404–8.
- Bellone RR, Liu J, Petersen JL, Mack M, Singer‐Berk M, Drögemüller C. A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses.. Int J Cancer 2017;141: 342–53.
- Singer-Berk M, Knickelbein KE, Vig S, Liu J, Bentley E, Nunnery C. Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.. Anim Genet 2018. Oct;49: 457–460.
- Giuliano EA, Johnson PJ, Delgado C, Pearce JW, Moore CP. Local photodynamic therapy delays recurrence of equine periocular squamous cell carcinoma compared to cryotherapy.. Vet Ophthalmol 2014;17: 37–45.
- Théon AP. Intralesional and topical chemotherapy and immunotherapy.. Vet Clin North Am Equine Pract 1998. Dec;14: 659–71, viii.
- Hewes CA, Sullins KE. Use of cisplatin-containing biodegradable beads for treatment of cutaneous neoplasia in equidae: 59 cases (2000–2004).. J Am Vet Med Assoc 2006;229: 1617–22.
- McCalla TL, Moore CP, Collier LL. Immunotherapy of periocular squamous cell carcinoma with metastasis in a pony.. J Am Vet Med Assoc 1992;200: 1678–1681.
- Grier RL, Brewer WG Jr, Paul SR. Treatment of bovine and equine ocular squamous cell carcinoma by radiofrequency hyper- thermia.. J Am Vet Med Assoc 1980;177: 55–61.
- Mosunic CB, Moore PA, Carmicheal KP. Effects of treatment with and without adjuvant radiation therapy on recurrence of ocular and adnexal squamous cell carcinoma in horses: 157 cases (1985–2002).. J Am Vet Med Assoc 2004;225: 1733–1738.
- Giuliano EA. Equine periocular neoplasia: current concepts in aetiopathogenesis and emerging treatment modalities.. Equine Vet J 2010;42: 9–18.
- Ferrantini M, Capone I, Belardelli F. Interferon-α and cancer: mechanisms of action and new perspectives of clinical use.. Biochimie 2007;89: 884–93.
- Gutterman JU. Cytokine therapeutics: lessons from interferon alpha.. Proc Natl Acad Sci U S A 1994. Feb 15;91: 1198–205.
- Ma H, Chang H, Yang W, Lu Y, Hu J, Jin S. A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma.. Mol Cancer 2020;19: 4.
- Kim HJ, Shields CL, Shah SU, Kaliki S, Lally SE. Giant ocular surface squamous neoplasia managed with interferon alpha-2b as immunotherapy or immunoreduction.. Ophthalmology 2012;119: 938–44.
- Park JO, Lee SI, Song SY, Kim K, Kim WS, Jung CW. Measuring response in solid tumors: comparison of RECIST and WHO response criteria.. Jpn J Clin Oncol 2003. Oct;33: 533–7.
- Antonelli G, Currenti M, Turriziani O, Dianzani F. Neutralizing antibodies to interferon-α: relative frequency in patients treated with different interferon preparations.. J Infect Dis 1991;163: 882–5.
- Milella M, Antoneill G, Santantonio T, Currenti M, Monno L, Mariano N. Neutralizing antibodies to recombinant alpha‐interferon and response to therapy in chronic hepatitis C virus infection.. Liver 1993;13: 146–150.
- Bertolotto A. Evaluation of the impact of neutralizing antibodies on IFNβ response.. Clin Chim Acta 2015;449: 31–36.
- Rönnblom LE, Janson ET, Perers A, Oberg KE, Alm GV. Characterization of anti‐interferon‐α antibodies appearing during recombinant interferon‐α2a treatment.. Clin Exp Immunol 1992;89: 330–335.
- Steis RG, Smith JW 2nd, Urba WJ, Venzon DJ, Longo DL, Barney R. Loss of interferon antibodies during prolonged continuous interferon-alpha 2a therapy in hairy cell leukemia.. Blood 1991. Feb 15;77: 792–8.
- Aruna, Li L. Anti-Interferon Alpha Antibodies in Patients with High-Risk BCR/ABL-Negative Myeloproliferative Neoplasms Treated with Recombinant Human Interferon-α.. Med Sci Monit 2018. Apr 17;24: 2302–2309.
- Dugan SJ, Roberts SM, Curtis CR. Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978–1988).. J Am Vet Med Assoc 1991;198: 298–303.
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