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

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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.

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Acknowledgements

The authors acknowledge and thank the clinical staff of the Colorado State University Veterinary Teaching Hospital who provided care and assisted with procedures described.

Funding

This study was funded by the Charles Shipley Family Foundation and by a grant from the Translational Medicine Institute and CSU Ventures at Colorado State University. Dr. Pezzanite was also supported by NIH grants 5TL1TR002533-02 and 5T32OD010437-19.

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Authors and Affiliations

  1. 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 L. Wotman, Lyndah Chow, Brittany Martabano, Lynn M. Pezzanite & Steven Dow

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  1. Kathryn L. Wotman
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  2. Lyndah Chow
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  3. Brittany Martabano
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  4. Lynn M. Pezzanite
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  5. Steven Dow
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by LC, KW, BM. All clinical trials and related sample collection were performed by KW, BM. LP performed manuscript writing and data verification. The final version of manuscript was approved by all authors.

Corresponding author

Correspondence to Kathryn L. Wotman.

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Competing interests

Authors Steven Dow and Lyndah Chow declare that they are among several holders of an issued US patent related to the LTC technology. All other authors declared no potential conflicts of interest.

Conflict of interest

The authors have read the journal’s policy and confirm that the ethical policies of the journal, as noted on the journal’s author guidelines page, have been adhered to. Owners provided consent for enrollment of client-owned patients in this clinical study. SD and LC declare that they are among several holders of an issued US patent related to the LTC technology. All other authors declared no potential conflicts of interest.

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Wotman, K.L., Chow, L., Martabano, B. et al. Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia. Cancer Immunol Immunother 72, 1185–1198 (2023). https://doi.org/10.1007/s00262-022-03321-2

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