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Home / Equine Research Bank / Cancer Immunol Immunother / Novel ocular immunotherapy induces tumor regression in an eq...
Cancer immunology, immunotherapy : CII2022; 72(5); 1185-1198; doi: 10.1007/s00262-022-03321-2

Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia.

Abstract: Ocular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of a liposomal TLR complex (LTC) immunotherapy, which previously demonstrated strong antiviral activity in multiple animal models following mucosal application, for ocular antitumor activity in a horse spontaneous OSSN model. In vitro studies demonstrated strong activation of interferon responses in horse leukocytes by LTC and suppression of OSSN cell growth and migration. In a trial of 8 horses (9 eyes), treatment with topical or perilesional LTC resulted in an overall tumor response rate of 67%, including durable regression of large OSSN tumors. Repeated treatment with LTC ocular immunotherapy was also very well tolerated clinically. We conclude therefore that ocular immunotherapy with LTC warrants further investigation as a novel approach to management of OSSN in humans.
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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Publication Date: 2022-11-11 PubMed ID: 36367558PubMed Central: 7509040DOI: 10.1007/s00262-022-03321-2Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper explores the effectiveness of a liposomal TLR complex (LTC) immunotherapy, initially recognized for its antiviral activity, in treating Ocular Surface Squamous Neoplasia (OSSN), a major cause of corneal cancer, using a horse model. Through in vitro studies and a trial involving horses, the team examines how LTC induces regression of OSSN tumors and its overall potential as a treatment option.

Introduction and Background

  • Ocular Surface Squamous Neoplasia (OSSN) is a common cause of corneal cancer in both humans and horses.
  • Increased global exposure to UVB radiation contributes to the growing prevalence of OSSN.
  • Currently, there are no officially approved treatments for OSSN, making it a significant health concern worldwide.

Investigating a Treatment Option

  • The researchers turned their attention to liposomal TLR complex (LTC) immunotherapy, which had demonstrated strong antiviral activity in previous studies, to investigate its potential as an ocular antitumor agent.
  • The teams conducted in vitro studies, observing that LTC strongly activated interferon responses in horse leukocytes and brought about suppression of OSSN cell growth and migration.

Trials and Results

  • A trial was conducted involving 8 horses (with a total of 9 eyes affected by OSSN).
  • Upon administering topical or perilesional LTC, they observed an overall tumor response rate of 67%. This included durable regression of large OSSN tumors, implying the treatment had a substantial impact.
  • Repeated use of LTC ocular immunotherapy was also well tolerated clinically, suggesting it could be a sustainable treatment option.

Conclusion

  • Based on their findings, the researchers concluded that LTC immunotherapy could hold promise as a novel approach to managing OSSN in humans.
  • The suggest that their research warrants further investigation into the application and effectiveness of this therapy in human OSSN patients.

Cite This Article

APA
Wotman KL, Chow L, Martabano B, Pezzanite LM, Dow S. (2022). Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia. Cancer Immunol Immunother, 72(5), 1185-1198. https://doi.org/10.1007/s00262-022-03321-2

Publication

Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
NlmUniqueID: 8605732
Country: Germany
Language: English
Volume: 72
Issue: 5
Pages: 1185-1198

Researcher Affiliations

Wotman, Kathryn L
  • Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA. Kathryn.Wotman@colostate.edu.
Chow, Lyndah
  • Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.
Martabano, Brittany
  • Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.
Pezzanite, Lynn M
  • Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.
Dow, Steven
  • Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.

MeSH Terms

  • Humans
  • Horses
  • Animals
  • Interferon alpha-2 / therapeutic use
  • Carcinoma, Squamous Cell / pathology
  • Antineoplastic Agents / therapeutic use
  • Conjunctival Neoplasms / drug therapy
  • Conjunctival Neoplasms / pathology
  • Conjunctival Neoplasms / surgery
  • Interferon-alpha
  • Eye Neoplasms / therapy
  • Immunotherapy
  • Retrospective Studies

Grant Funding

  • 5TL1TR002533-02 / NIH HHS

References

This article includes 54 references
  1. Kafarnik C, Rawlings M, Dubielzig RR. Corneal stromal invasive squamous cell carcinoma: a retrospective morphological description in 10 horses.. Vet Ophthalmol 2009 Jan-Feb;12(1):6-12.
    pubmed: 19152592doi: 10.1111/j.1463-5224.2009.00666.xgoogle scholar: lookup
  2. Wilcock BP. The eye and ear. Pathology of domestic animals pp 441–529.
  3. Blodi FC, Ramsey FK. Ocular tumors in domestic animals. Am J Ophthalmol 64(3):627–633.
    doi: 10.1016/0002-9394(67)90568-5google scholar: lookup
  4. McInnis CL, Giuliano EA, Johnson PJ, Turk JR. Immunohistochemical evaluation of cyclooxygenase expression in corneal squamous cell carcinoma in horses.. Am J Vet Res 2007 Feb;68(2):165-70.
    pubmed: 17269882doi: 10.2460/ajvr.68.2.165google scholar: lookup
  5. Dugan SJ, Curtis CR, Roberts SM, Severin GA. Epidemiologic study of ocular/adnexal squamous cell carcinoma in horses.. J Am Vet Med Assoc 1991 Jan 15;198(2):251-6.
    pubmed: 2004985
  6. Sykora S, Brandt S. Papillomavirus infection and squamous cell carcinoma in horses.. Vet J 2017 May;223:48-54.
    pubmed: 28671071doi: 10.1016/j.tvjl.2017.05.007google scholar: lookup
  7. Rassnick KM, Njaa BL. Cyclooxygenase-2 immunoreactivity in equine ocular squamous-cell carcinoma.. J Vet Diagn Invest 2007 Jul;19(4):436-9.
    pubmed: 17609359doi: 10.1177/104063870701900419google scholar: lookup
  8. Dugan SJ, Roberts SM, Curtis CR, Severin GA. Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978-1988).. J Am Vet Med Assoc 1991 Jan 15;198(2):298-303.
    pubmed: 2004996
  9. 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 Nov;23(6):449-52.
    pubmed: 1778163doi: 10.1111/j.2042-3306.1991.tb03759.xgoogle scholar: lookup
  10. Mosunic CB, Moore PA, Carmicheal KP, Chandler MJ, Vidyashankar A, Zhao Y, Roberts RE, Dietrich UM. 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 Dec 1;225(11):1733-8.
    pubmed: 15626225doi: 10.2460/javma.2004.225.1733google scholar: lookup
  11. McCalla TL, Moore CP, Collier LL. Immunotherapy of periocular squamous cell carcinoma with metastasis in a pony.. J Am Vet Med Assoc 1992 Jun 1;200(11):1678-81.
    pubmed: 1624344
  12. Théon AP, Pascoe JR, Meagher DM. Perioperative intratumoral administration of cisplatin for treatment of cutaneous tumors in equidae.. J Am Vet Med Assoc 1994 Oct 15;205(8):1170-6.
    pubmed: 7890578
  13. Théon AP, Pascoe JR. Iridium-192 interstitial brachytherapy for equine periocular tumours: treatment results and prognostic factors in 115 horses.. Equine Vet J 1995 Mar;27(2):117-21.
    pubmed: 7607143doi: 10.1111/j.2042-3306.1995.tb03046.xgoogle scholar: lookup
  14. Théon AP, Pascoe JR, Madigan JE, Carlson G, Metzger L. Comparison of intratumoral administration of cisplatin versus bleomycin for treatment of periocular squamous cell carcinomas in horses.. Am J Vet Res 1997 Apr;58(4):431-6.
    pubmed: 9099393
  15. Wilkie DA, Burt JK. Combined treatment of ocular squamous cell carcinoma in a horse, using radiofrequency hyperthermia and interstitial 198Au implants.. J Am Vet Med Assoc 1990 Jun 1;196(11):1831-3.
    pubmed: 2351606
  16. English RV, Nasisse MP, Davidson MG. Carbon dioxide laser ablation for treatment of limbal squamous cell carcinoma in horses.. J Am Vet Med Assoc 1990 Feb 1;196(3):439-42.
    pubmed: 2298673
  17. Walker MA, Schumacher J, Schmitz DG, McMullen WC, Ruoff WW, Crabill MR, Hawkins JF, Hogan PM, McClure SR, Vacek JR, Edwards JF, Helman RG, Frelier PF. Cobalt 60 radiotherapy for treatment of squamous cell carcinoma of the nasal cavity and paranasal sinuses in three horses.. J Am Vet Med Assoc 1998 Mar 15;212(6):848-51.
    pubmed: 9530425
  18. De Ridder T, Ruppin M, Wheeless M, Williams S, Reddell P. Use of the Intratumoural Anticancer Drug Tigilanol Tiglate in Two Horses.. Front Vet Sci 2020;7:639.
    pubmed: 33033726pmc: 7509040doi: 10.3389/fvets.2020.00639google scholar: lookup
  19. Estell K. Periocular Neoplasia in the Horse.. Vet Clin North Am Equine Pract 2017 Dec;33(3):551-562.
    pubmed: 29103561doi: 10.1016/j.cveq.2017.08.004google scholar: lookup
  20. Elce YA, Orsini JA, Blikslager AT. Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell carcinomas in horses.. Am J Vet Res 2007 Jan;68(1):76-80.
    pubmed: 17199422doi: 10.2460/ajvr.68.1.76google scholar: lookup
  21. Howarth S, Lucke VM, Pearson H. Squamous cell carcinoma of the equine external genitalia: a review and assessment of penile amputation and urethrostomy as a surgical treatment.. Equine Vet J 1991 Jan;23(1):53-8.
    pubmed: 2015809doi: 10.1111/j.2042-3306.1991.tb02715.xgoogle scholar: lookup
  22. Hendrix DVH. Equine ocular squamous cell carcinoma. Clin Tech Equine Pract 4(1):87–94.
    doi: 10.1053/j.ctep.2005.03.011google scholar: lookup
  23. Gichuhi S, Ohnuma S, Sagoo MS, Burton MJ. Pathophysiology of ocular surface squamous neoplasia.. Exp Eye Res 2014 Dec;129:172-82.
    pubmed: 25447808pmc: 4726664doi: 10.1016/j.exer.2014.10.015google scholar: lookup
  24. Shank AMM, Teixeria LBC, Dubielzig RR. Canine, feline, and equine corneal vascular neoplasia: A retrospective study (2007-2015).. Vet Ophthalmol 2019 Jan;22(1):76-87.
    doi: 10.1111/vop.12571pubmed: 29689619google scholar: lookup
  25. Crausaz M, Launois T, Smith-Fleming K, McCoy AM, Knickelbein KE, Bellone RR. DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds.. Genes (Basel) 2020 Dec 5;11(12).
    doi: 10.3390/genes11121460pubmed: 33291392google scholar: lookup
  26. Bellone RR. Genetics of equine ocular disease. Vet Clin N Am Equine Pract 36(2):303–322.
    doi: 10.1016/j.cveq.2020.03.009google scholar: lookup
  27. Bellone RR, Liu J, Petersen JL, Mack M, Singer-Berk M, Drögemüller C, Malvick J, Wallner B, Brem G, Penedo MC, Lassaline M. 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 Jul 15;141(2):342-353.
    pubmed: 28425625doi: 10.1002/ijc.30744google scholar: lookup
  28. Knickelbein KE, Lassaline ME, Singer-Berk M, Reilly CM, Clode AB, Famula TR, Michau TM, Bellone RR. A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for ocular squamous cell carcinoma in Belgian horses.. Equine Vet J 2020 Jan;52(1):34-40.
    pubmed: 30903710doi: 10.1111/evj.13116google scholar: lookup
  29. Neale RE, Weissenborn S, Abeni D, Bavinck JN, Euvrard S, Feltkamp MC, Green AC, Harwood C, de Koning M, Naldi L, Nindl I, Pawlita M, Proby C, Quint WG, Waterboer T, Wieland U, Pfister H. Human papillomavirus load in eyebrow hair follicles and risk of cutaneous squamous cell carcinoma.. Cancer Epidemiol Biomarkers Prev 2013 Apr;22(4):719-27.
    pubmed: 23396961doi: 10.1158/1055-9965.EPI-12-0917-Tgoogle scholar: lookup
  30. Zhu KW, Affolter VK, Gaynor AM, Dela Cruz FN Jr, Pesavento PA. Equine Genital Squamous Cell Carcinoma: In Situ Hybridization Identifies a Distinct Subset Containing Equus caballus Papillomavirus 2.. Vet Pathol 2015 Nov;52(6):1067-72.
    pubmed: 25967135doi: 10.1177/0300985815583095google scholar: lookup
  31. Wheat W, Chow L, Coy J, Contreras E, Lappin M, Dow S. Activation of upper respiratory tract mucosal innate immune responses in cats by liposomal toll-like receptor ligand complexes delivered topically.. J Vet Intern Med 2019 Mar;33(2):838-845.
    pubmed: 30770582pmc: 6430862doi: 10.1111/jvim.15426google scholar: lookup
  32. Wheat W, Chow L, Kuzmik A, Soontararak S, Kurihara J, Lappin M, Dow S. Local immune and microbiological responses to mucosal administration of a Liposome-TLR agonist immunotherapeutic in dogs.. BMC Vet Res 2019 Sep 13;15(1):330.
    pubmed: 31519215pmc: 6743184doi: 10.1186/s12917-019-2073-8google scholar: lookup
  33. Wheat W, Chow L, Rozo V, Herman J, Still Brooks K, Colbath A, Hunter R, Dow S. Non-specific protection from respiratory tract infections in cattle generated by intranasal administration of an innate immune stimulant.. PLoS One 2020;15(6):e0235422.
    pubmed: 32584899pmc: 7316291doi: 10.1371/journal.pone.0235422google scholar: lookup
  34. Zaks K, Jordan M, Guth A, Sellins K, Kedl R, Izzo A, Bosio C, Dow S. Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes.. J Immunol 2006 Jun 15;176(12):7335-45.
    pubmed: 16751377doi: 10.4049/jimmunol.176.12.7335google scholar: lookup
  35. Kamstock D, Guth A, Elmslie R, Kurzman I, Liggitt D, Coro L, Fairman J, Dow S. Liposome-DNA complexes infused intravenously inhibit tumor angiogenesis and elicit antitumor activity in dogs with soft tissue sarcoma.. Cancer Gene Ther 2006 Mar;13(3):306-17.
    pubmed: 16138118doi: 10.1038/sj.cgt.7700895google scholar: lookup
  36. Regan D, Dow S. Manipulation of Innate Immunity for Cancer Therapy in Dogs.. Vet Sci 2015 Dec 1;2(4):423-439.
    doi: 10.3390/vetsci2040423pubmed: 29061951pmc: 5644648google scholar: lookup
  37. Eaton JS, Miller PE, Bentley E, Thomasy SM, Murphy CJ. The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology.. J Ocul Pharmacol Ther 2017 Dec;33(10):718-734.
    pubmed: 29239680doi: 10.1089/jop.2017.0108google scholar: lookup
  38. van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay.. Methods Mol Biol 2011;731:237-45.
    pubmed: 21516412doi: 10.1007/978-1-61779-080-5_20google scholar: lookup
  39. Henderson A, Propst K, Kedl R, Dow S. Mucosal immunization with liposome-nucleic acid adjuvants generates effective humoral and cellular immunity.. Vaccine 2011 Jul 18;29(32):5304-12.
    pubmed: 21600950pmc: 3539814doi: 10.1016/j.vaccine.2011.05.009google scholar: lookup
  40. Aricò E, Castiello L, Capone I, Gabriele L, Belardelli F. Type I Interferons and Cancer: An Evolving Story Demanding Novel Clinical Applications.. Cancers (Basel) 2019 Dec 4;11(12).
    doi: 10.3390/cancers11121943pubmed: 31817234google scholar: lookup
  41. Chulpanova DS, Kitaeva KV, Green AR, Rizvanov AA, Solovyeva VV. Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy.. Front Cell Dev Biol 2020;8:402.
    pubmed: 32582698pmc: 7283917doi: 10.3389/fcell.2020.00402google scholar: lookup
  42. Alexandroff AB, Jackson AM, O'Donnell MA, James K. BCG immunotherapy of bladder cancer: 20 years on.. Lancet 1999 May 15;353(9165):1689-94.
    doi: 10.1016/S0140-6736(98)07422-4pubmed: 10335805google scholar: lookup
  43. Studer U, Marti E, Stornetta D, Lazary S, Gerber H. The therapy of equine sarcoid with a non-specific immunostimulator—the epidemiology and spontaneous regression of sarcoids. (0036–7281 (Print)).
  44. Papaioannou NE, Beniata OV, Vitsos P, Tsitsilonis O, Samara P. Harnessing the immune system to improve cancer therapy.. Ann Transl Med 2016 Jul;4(14):261.
    pubmed: 27563648pmc: 4971375doi: 10.21037/atm.2016.04.01google scholar: lookup
  45. Dow SW, Fradkin LG, Liggitt DH, Willson AP, Heath TD, Potter TA. Lipid-DNA complexes induce potent activation of innate immune responses and antitumor activity when administered intravenously.. J Immunol 1999 Aug 1;163(3):1552-61.
    pubmed: 10415059doi: 10.4049/jimmunol.163.3.1552google scholar: lookup
  46. Dow S. Liposome-nucleic acid immunotherapeutics.. Expert Opin Drug Deliv 2008 Jan;5(1):11-24.
    pubmed: 18095926pmc: 3539802doi: 10.1517/17425247.5.1.11google scholar: lookup
  47. Boukhaled GM, Harding S, Brooks DG. Opposing Roles of Type I Interferons in Cancer Immunity.. Annu Rev Pathol 2021 Jan 24;16:167-198.
    pubmed: 33264572doi: 10.1146/annurev-pathol-031920-093932google scholar: lookup
  48. Cao X, Liang Y, Hu Z, Li H, Yang J, Hsu EJ, Zhu J, Zhou J, Fu YX. Next generation of tumor-activating type I IFN enhances anti-tumor immune responses to overcome therapy resistance.. Nat Commun 2021 Oct 7;12(1):5866.
    pubmed: 34620867pmc: 8497482doi: 10.1038/s41467-021-26112-2google scholar: lookup
  49. Budhwani M, Mazzieri R, Dolcetti R. Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance.. Front Oncol 2018;8:322.
    pubmed: 30186768pmc: 6110817doi: 10.3389/fonc.2018.00322google scholar: lookup
  50. Liu Y, Chen Z, Qiu J, Chen H, Zhou Z. Altered Tim-1 and IL-10 Expression in Regulatory B Cell Subsets in Type 1 Diabetes.. Front Immunol 2021;12:773896.
    doi: 10.3389/fimmu.2021.620284pubmed: 35754999pmc: 8750059google scholar: lookup
  51. Gao A, Hu XL, Saeed M, Chen BF, Li YP, Yu HJ. Overview of recent advances in liposomal nanoparticle-based cancer immunotherapy.. Acta Pharmacol Sin 2019 Sep;40(9):1129-1137.
    pubmed: 31371782pmc: 6786406doi: 10.1038/s41401-019-0281-1google scholar: lookup
  52. Galor A, Karp CL, Chhabra S, Barnes S, Alfonso EC. Topical interferon alpha 2b eye-drops for treatment of ocular surface squamous neoplasia: a dose comparison study.. Br J Ophthalmol 2010 May;94(5):551-4.
    pubmed: 19493859doi: 10.1136/bjo.2008.153197google scholar: lookup
  53. Al Bayyat G, Arreaza-Kaufman D, Venkateswaran N, Galor A, Karp CL. Update on pharmacotherapy for ocular surface squamous neoplasia. Eye Vis 6(1):24.
    doi: 10.1186/s40662-019-0150-5google scholar: lookup
  54. Kozma K, Dömötör ZR, Csutak A, Szabó L, Hegyi P, Erőss B, Helyes Z, Molnár Z, Dembrovszky F, Szalai E. Topical pharmacotherapy for ocular surface squamous neoplasia: systematic review and meta-analysis.. Sci Rep 2022 Aug 20;12(1):14221.
    pubmed: 35987957pmc: 9392743doi: 10.1038/s41598-022-18545-6google scholar: lookup

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