Abstract: Intralesional chemotherapeutic administration represents an important treatment option for equine cutaneous neoplasia. Tigilanol-tiglate (TT), a novel molecule extracted from Fontainea picrosperma, an Australian rainforest plant, is registered for intratumoural treatment of canine MCT, leading to rapid oncosis and tumour slough. Evidence from horses is limited but suggests that efficacy may be similar. Objective: To evaluate the response to intratumoural TT treatment in horses with sarcoids (fibroblastic/nodular) and cutaneous melanomas. Methods: Two noncontrolled prospective multicentre clinical trials, one for each of sarcoids and melanomas. Methods: Cases were enrolled across multiple sites and treated by the same site-specific clinician with intralesional TT (sarcoids: 0.35 mg/cm3; melanomas: 0.2 mg/cm3 of tumour volume - Tvol; max dose 2 mg). Quantitative (Tvol regression) and qualitative outcomes (likely tumour free (LTF) per expert opinion) were recorded, and potential determinants of efficacy were assessed using random effects logistic models. A full clinical response was complete Tvol regression and a LTF treatment site. Results: Forty-one sarcoids and 97 melanomas were enrolled and treated. 73/74% of treated sarcoids/melanomas showed complete Tvol regression. 64/61% (sarcoids/melanomas) showed a full clinical response at medians of 546/247 days post final treatment. For both tumour types, this response was dependent on initial tumour volume (Psarcoids = 0.006; Pmelanomas <0.001). The predicted probability of a full clinical response was 6 times greater for initially small sarcoids (Tvol = 1 cm3) than for the maximum study volume (Tvol = 6 cm3). For melanomas in the perineal region, this was 11 times greater for Tvol ≤0.3 cm3 than for tumours ≥2.0 cm3. For melanomas, tumour location further affected treatment efficacy = 0.005). In total, 5 adverse events were reported. Conclusions: Lack of treatment control and histologic/biomolecular follow-up data. Conclusions: The observed therapeutic efficacy of TT supports clinical use as well as early interventions in horses. Successful use necessitates knowledge of the drug's mode of action and management of associated local site responses. Unassigned: Die intraläsionale Verabreichung von Chemotherapeutika stellt eine wichtige Behandlungsoption für kutane Neoplasien bei Pferden dar. Tigilanol‐Tiglat (TT), eine neuartige Molekülverbindung, die aus Fontainea picrosperma, einer australischen Regenwaldpflanze, extrahiert wird, ist für die intratumorale Behandlung von Mastzelltumoren (MCT) in Hunden zugelassen und führt zu einer schnellen Onkose und Tumorablösung. Die Evidenzlage bei Pferden ist begrenzt, deutet jedoch auf eine ähnliche Wirksamkeit hin. Unassigned: Bewertung der Wirksamkeit der intratumoralen TT‐Behandlung bei Pferden mit Sarkoiden (fibroblastisch/nodulär) und kutanen Melanomen. Methods: Zwei nicht‐kontrollierte, prospektive multizentrische klinische Studien, jeweils eine für Sarkoide und eine für Melanome. Methods: Fälle wurden an mehreren Standorten rekrutiert und von standortspezifischen Klinikern mit intraläsionalem TT behandelt (Sarkoide: 0,35 mg/cm3; Melanome: 0,2 mg/cm3 Tumorvolumen – Tvol; max. Dosis 2 mg). Quantitative (Tvol‐Regression) und qualitative Ergebnisse (wahrscheinlich tumorfreies (LTF) Behandlungsgebiet nach Experteneinschätzung) wurden erfasst, und potenzielle Einflussfaktoren auf die Wirksamkeit wurden mittels logistischer Zufallseffekte‐Modelle analysiert. Eine vollständige klinische Entfernung wurde als komplette Tvol‐Regression und ein LTF‐Behandlungsgebiet definiert. Results: Insgesamt wurden 41 Sarkoide und 97 Melanome behandelt. 73% bzw. 74% der behandelten Sarkoide bzw. Melanome zeigten eine vollständige Tvol‐Regression. 64% bzw. 61% (Sarkoide/Melanome) zeigten eine vollständige klinische Entfernung nach einem medianen Zeitraum von 546 bzw. 247 Tagen nach der letzten Behandlung. Bei beiden Tumortypen war die Reaktion abhängig vom initialen Tumorvolumen (PsarCoid = 0,006; Pmelanomas <0,001). Die vorhergesagte Wahrscheinlichkeit einer vollständigen klinischen Entfernung war für kleine initiale Sarkoide (Tvol = 1 cm3) sechsmal höher als für das maximale untersuchte Volumen (Tvol = 6 cm3). Bei Melanomen in der Perinealregion war diese Wahrscheinlichkeit bei Tvol ≤0,3 cm3 elfmal höher als bei Tumoren ≥2,0 cm3. Für Melanome beeinflusste zudem die Tumorlokalisation die Therapieeffektivität (P = 0,005). Insgesamt wurden fünf unerwünschte Ereignisse gemeldet. WICHTIGSTE EINSCHRÄNKUNGEN: Fehlende Kontrollgruppe sowie keine histologischen/biomolekularen Nachverfolgungsdaten. Unassigned: Die beobachtete therapeutische Wirksamkeit von TT unterstützt die klinische Anwendung und frühzeitige Interventionen bei Pferden. Eine erfolgreiche Anwendung erfordert Kenntnisse über den Wirkmechanismus des Medikaments sowie das Management der lokalen Gewebereaktionen.
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The research explores the use of tigilanol-tiglate (TT), a substance from the Australian rainforest plant Fontainea picrosperma, as a treatment for equine sarcoids and cutaneous melanomas. The intralesional administration of this substance has shown promise in studies on horses, demonstrating efficacy in tumor regression and the potential for a tumor-free condition.
Objective and Methodology
The aim of the research is to assess the impact of intratumoural TT treatment on horses suffering from fibroblastic/nodular sarcoids and cutaneous melanomas.
Two non-controlled prospective multicentre clinical trials were conducted, one for sarcoids and another for melanomas.
Cases were enrolled across multiple sites and treated by the same clinician with intralesional TT. The dosage used was 0.35 mg/cm for sarcoids and 0.2 mg/cm of tumour volume for melanomas, with a maximum dose of 2 mg.
The team used random effects logistic models to assess potential determinants of efficacy.
The quantitative and qualitative outcomes were recorded. A complete clinical response was defined as complete T regression and a Likely Tumour Free (LTF) treatment site.
Results
Out of 41 sarcoids and 97 melanomas that were enrolled and treated, 73/74% showed complete regression. Full clinical response was seen in 64/61% of sarcoids/melanomas at medians of 546/247 days post final treatment.
The research shows that the response to treatment was dependent on the initial tumor volume. The predicted probability of a full clinical response was 6 times greater for initially small sarcoids and 11 times greater for small melanomas in the perineal region.
The location of the melanoma was also observed to affect treatment efficacy.
The researchers reported five adverse events during the course of treatment.
Conclusion
The study concluded that TT treatment has therapeutic efficacy and supports its clinical use as well as early interventions in horses.
The limitation of the study includes lack of control group and follow-up histologic/biomolecular data.
The study advices that successful use of the TT treatment requires understanding its mode of action and managing the local site responses.
Cite This Article
APA
Labens R, Saba C, Williams J, Hollis A, Ensink J, José-Cunilleras ELV, Jordana-Garcia M, Bergvall K, Ruppin M, Condon F, Spelta C, Elce Y, De Ridder T, Morton J, McGee C, Reddell P.
(2025).
Intratumoural tigilanol tiglate in the multicentre treatment of equine sarcoids and cutaneous melanomas.
Equine Vet J.
https://doi.org/10.1111/evj.14502
Panizza BJ, de Souza P, Cooper A, Roohullah A, Karapetis CS, Lickliter JD. Phase I dose‐escalation study to determine the safety, tolerability, preliminary efficacy and pharmacokinetics of an intratumoral injection of tigilanol tiglate (EBC‐46).. EBioMedicine 2019;50:433–441.
Cullen JK, Boyle GM, Yap PY, Elmlinger S, Simmons JL, Broit N. Activation of PKC supports the anticancer activity of tigilanol tiglate and related epoxytiglianes.. Sci Rep 2021;11:207.
Reddell P, De Ridder TR, Morton JM, Jones PD, Campbell JE, Brown G. 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;35:430–441.
De Ridder TR, Campbell JE, Burke‐Schwarz C, Clegg D, Elliot EL, Geller S. Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate (EBC‐46).. J Vet Intern Med 2021;35:415–429.
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.
Powell LC, Cullen JK, Boyle GM, De Ridder T, Yap PY, Xue W. Topical, immunomodulatory epoxy‐tiglianes induce biofilm disruption and healing in acute and chronic skin wounds.. Sci Transl Med 2022;14:eabn3758.
Noordwijk K, Boone L, Hanson R. Tigilanol tiglate in the treatment of perineal squamous cell carcinoma in the horse.. Valencia: European College of Veterinary Surgeons; 2024.
Graner A, Epke B, Meyer L. The use of tigilanol tiglate in two horses with mastcell tumors.. Der Prakt Tierarzt 2021;102:1297ff.
Monga SP, Wadleigh R, Sharma A, Adib H, Strader D, Singh G. Intratumoral therapy of cisplatin/epinephrine injectable gel for palliation in patients with obstructive esophageal cancer.. Am J Clin Oncol 2000;23:386–392.
Celikoglu F, Celikoglu SI, Goldberg EP. Techniques for intratumoral chemotherapy of lung cancer by bronchoscopic drug delivery.. Cancer Therapy 2008;6:287–295.
Koch C, Martens A, Hainisch EK, Schüpbach G, Gerber V, Haspeslagh M. The clinical diagnosis of equine sarcoids—part 1: assessment of sensitivity and specificity using a multicentre case‐based online examination.. Vet J 2018;242:77–82.
Martens A, Moor A, Demeulemeester J, Ducatelle R. Histopathological characteristics of five clinical types of equine sarcoid.. Res Vet Sci 2000;69:295–300.
Cullen JK, Yap P‐Y, Ferguson B, Bruce ZC, Koyama M, Handoko H. 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;12(4):e006602.
Boyle GM, D'Souza MM, Pierce CJ, Adams RA, Cantor AS, Johns JP. Intra‐lesional injection of the novel PKC activator EBC‐46 rapidly ablates tumors in mouse models.. PLoS One 2014;9:e108887.
Pol JG, Lizarralde‐Guerrero M, Kroemer G. Immunogenic oncolysis by tigilanol tiglate.. Onco Targets Ther 2024;13:2360230.
Bartlett EK, Li DG, Shemla S, Ariyan CE, Dickinson S, Crago A. A pilot phase II study to evaluate the small molecule tigilanol tiglate in patients with advanced soft tissue sarcoma (NCT05755113).. Barcelona: European Society for Medical Oncology (ESMO); 2024. p. 1736P.
Pettersson CM, Broström H, Humblot P, Bergvall KE. Topical treatment of equine sarcoids with imiquimod 5% cream or Sanguinaria canadensis and zinc chloride—an open prospective study.. Vet Dermatol 2020;31:471‐e126.