Use of the Intratumoural Anticancer Drug Tigilanol Tiglate in Two Horses.
Abstract: Tigilanol tiglate is a novel small molecule approved as a veterinary pharmaceutical in Europe for intratumoural treatment of non-metastatic, non-resectable canine mast cell tumors. The drug has a "tumor agnostic" mode of action associated with induction of an acute inflammatory response at the treatment site, immune cell recruitment, and disruption of tumor vasculature. Consequently, tigilanol tiglate has potential in treating a range of tumor types in humans and companion animals. However, it is likely that species-specific dosing and concomitant medication protocols will be required, especially to manage the drug-induced acute inflammatory response at the treatment site. As an initial step in evaluating tigilanol tiglate for treating cutaneous tumors in horses, we developed an equine-specific protocol involving (a) a 30% reduction in intratumoural tigilanol tiglate dose rate compared to that used in dogs, and (b) a regime of concomitant medications to manage the drug-induced acute inflammatory response at the treatment site. Here we report a preliminary study in two horses using the protocol to treat (i) an aggressive fibroblastic sarcoid that had recurred following surgical excision and (ii) a fast-growing peri-ocular squamous cell carcinoma. Clinical response to tigilanol tiglate treatment in these cases was similar to that observed in canine and human patients. Localized inflammation and bruising developed rapidly at the treatment site with haemorrhagic necrosis of the tumor evident within 24 h. Slough of necrotic tumor mass occurred within 6-16 days followed by infill of the tissue defect and full re-epithelialisation of the treatment site with good functional outcome. Drug-induced inflammation and oedema at the treatment site were well controlled by the concomitant medications and largely resolved within 3 days, while the wound that formed following tumor slough healed uneventfully. Both patients displayed minor lethargy during the first 36 h after treatment and localized treatment-site discomfort was apparent over the first 3-5 days. There was no evidence of recurrence of the sarcoid at 93 days, or the squamous cell carcinoma at 189 days. The results from this study support continued development and evaluation of tigilanol tiglate as a potential future treatment option for cutaneous equine tumors.
Copyright © 2020 De Ridder, Ruppin, Wheeless, Williams and Reddell.
Publication Date: 2020-09-09 PubMed ID: 33033726PubMed Central: PMC7509040DOI: 10.3389/fvets.2020.00639Google Scholar: Lookup
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Summary
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The research focus on the use of a novel veterinary anti-cancer drug, Tigilanol Tiglate, in the treatment of non-resectable tumors in horses. Initial results indicate that it effectively induced necrosis and the following healing of tumors, with minor side effects, in two equine cases examined.
Understanding Tigilanol Tiglate
- Tigilanol Tiglate is a new small molecule drug, approved for veterinary use in Europe, primarily indicated for the intratumoural treatment of non-metastatic, non-resectable canine mast cell tumors.
- Unlike many anticancer drugs, the mode of action of Tigilanol tiglate is “tumor-agnostic”, meaning it induces inflammation, immune cell recruitment, and disrupts tumor vasculature, regardless of tumor type.
- These qualities suggest it could be adapted for use in treating a variety of tumor types in humans and companion animals, including horses. However, appropriate dosing and co-administration protocols will need to be developed to manage the acute inflammatory response elicited by the drug.
Study Focus and Methodology
- The researchers sought to study the application and effects of Tigilanol Tiglate in treating cutaneous tumors in horses.
- Adjustments were made to the typical canine treatment protocol to suit horses; including reducing the intratumoural Tigilanol Tiglate dose by 30% and devising a regimen of co-administered medications to manage the drug-induced inflammatory response.
- The researchers conducted a preliminary study on two horses, one presenting a recurring fibroblastic sarcoid and the second a fast-growing peri-ocular squamous cell carcinoma.
Results and Observations
- The treatment response in the horses was similar to previous observations in dogs and humans, with rapid development of localized inflammation and bruising, followed by hemorrhagic necrosis of the tumor within 24 hours.
- After 6 to 16 days, the necrotic tumor mass sloughed off, leaving a tissue defect which proceeded to heal and fully re-epithelialise, leading to a positive functional outcome.
- The acute inflammation and swelling was generally well controlled by the co-administered medications and subsided within about three days, while any resulting wound went on to heal without complications.
- For both the cases, the horses presented minor lethargy for the first 36 hours post treatment and localized discomfort at the treatment site for the first 3-5 days.
- No signs of tumor recurrence were observed 93 days post treatment for the horse with the fibroblastic sarcoid, and after 189 days for the horse with the squamous cell carcinoma.
Future Implications
- The positive results obtained from this preliminary study suggest that continued research and development of Tigilanol Tiglate as a potential treatment option for certain types of equine tumors would be beneficial.
- Careful attention should be paid in future studies to managing the side effects of treatment, including inflammation, swelling, lethargy, and discomfort at the site of treatment.
Cite This Article
APA
De Ridder T, Ruppin M, Wheeless M, Williams S, Reddell P.
(2020).
Use of the Intratumoural Anticancer Drug Tigilanol Tiglate in Two Horses.
Front Vet Sci, 7, 639.
https://doi.org/10.3389/fvets.2020.00639 Publication
Researcher Affiliations
- QBiotics Group Ltd., Yungaburra, QLD, Australia.
- Tableland Veterinary Service, Malanda, QLD, Australia.
- Tableland Veterinary Service, Edmonton, QLD, Australia.
- Tableland Veterinary Service, Edmonton, QLD, Australia.
- QBiotics Group Ltd., Yungaburra, QLD, Australia.
References
This article includes 12 references
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Citations
This article has been cited 8 times.- Labens R, Saba C, Williams J, Hollis A, Ensink J, Jose-Cunilleras E, Jordana-Garcia M, Bergvall K, Ruppin M, Condon F, Spelta C, Elce Y, De Ridder T, Morton J, McGee C, Reddell P. Intratumoural tigilanol tiglate in the multicentre treatment of equine sarcoids and cutaneous melanomas. Equine Vet J 2026 Jan;58(1):89-104.
- Chow L, Flaherty E, Pezzanite L, Williams M, Dow S, Wotman K. Impact of Equine Ocular Surface Squamous Neoplasia on Interactions between Ocular Transcriptome and Microbiome. Vet Sci 2024 Apr 7;11(4).
- Cullen JK, Yap PY, Ferguson B, Bruce ZC, Koyama M, Handoko H, Hendrawan K, Simmons JL, Brooks KM, Johns J, Wilson ES, de Souza MMA, Broit N, Stewart P, Shelley D, McMahon T, Ogbourne SM, Nguyen TH, Lim YC, Pagani A, Appendino G, Gordon VA, Reddell PW, Boyle GM, Parsons PG. Tigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade. J Immunother Cancer 2024 Apr 24;12(4).
- Wotman KL, Chow L, Martabano B, Pezzanite LM, Dow S. Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia. Cancer Immunol Immunother 2023 May;72(5):1185-1198.
- Mitu SA, Stewart P, Tran TD, Reddell PW, Cummins SF, Ogbourne SM. Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma. Molecules 2022 Jun 21;27(13).
- De Ridder T, Reddell P, Jones P, Brown G, Campbell J. Tigilanol Tiglate-Mediated Margins: A Comparison With Surgical Margins in Successful Treatment of Canine Mast Cell Tumours. Front Vet Sci 2021;8:764800.
- Mitu SA, Ogbourne SM, Klein AH, Tran TD, Reddell PW, Cummins SF. The P450 multigene family of Fontainea and insights into diterpenoid synthesis. BMC Plant Biol 2021 Apr 20;21(1):191.
- Reddell P, De Ridder TR, Morton JM, Jones PD, Campbell JE, Brown G, Johannes CM, Schmidt PF, Gordon V. Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate. J Vet Intern Med 2021 Jan;35(1):430-441.
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