Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate
Open Access
- 31 January 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 37 (1), 1-8
- https://doi.org/10.1007/s10637-018-0604-y
Abstract
The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at 50% for the past 30years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1(nu) and NOD/SCID mice and treated with intratumoral injection of 30 g TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1(nu) mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.Keywords
Funding Information
- Princess Alexandra Hospital Research Foundation
- Queensland Head and Neck Cancer Centre
- QBiotics Ltd
This publication has 15 references indexed in Scilit:
- Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse ModelsPLOS ONE, 2014
- CyclodextrinsInternational Journal of Pharmaceutics, 2013
- Head and neck cancer: from anatomy to biologyInternational Journal of Cancer, 2013
- Antiangiogenesis Targeting Tumor Microenvironment Synergizes Glucuronide Prodrug Antitumor ActivityClinical Cancer Research, 2009
- Intratumoral rhIL‐12 administration in head and neck squamous cell carcinoma patients induces B cell activationInternational Journal of Cancer, 2008
- Standard, and novel cytotoxic and molecular-targeted, therapies for HNSCC: an evidence-based reviewCurrent Opinion in Oncology, 2007
- Intratumoral injection of herpes simplex virus HF10 in recurrent head and neck squamous cell carcinomaActa Oto-Laryngologica, 2006
- Intratumor Injections of Cisplatin and Laser Thermal Therapy for Palliative Treatment of Recurrent CancerPhotomedicine and Laser Surgery, 2005
- Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double‐blind, phase III study in North AmericaHead & Neck, 2003