Abstract LB-233: Microfragmented adipose tissue drug delivery in dog's mesothelioma
Authors: Zeira Offer , Ghezzi Erica , Pettinari Letizia , Re Valentina , Lupi Davide , Benali Silvia , Borgonovo Simone , Alessandri Giulio , Petrella Francesco , Paroni Rita , Deicas Michele , Tremolada Carlo , Ponzoni Mirco , Coccè Valentina , Pessina Augusto 
Published: September 2020

Abstract
Introduction. The aim of our study is to verify safety, feasibility and efficacy of intracavitary administration of Paclitaxel (PTX) loaded microfragmented adipose tissue (MFAT) in dog's mesothelioma. Mesothelioma is a rare neoplasm of dogs and humans, affecting the lining epithelial cells of the coelomic cavities of the body. It has no effective therapeutic strategies. In human medicine, median survival is 8-18 months, in veterinary medicine reported survival time is from 2 to 13 months. MFAT is a potential drug delivery medium that may provide slow release of chemotherapic drug contiguous to the tumor. Material and methods. In order to obtain MFAT, we employed a commercially available, enzyme free technology (LG). This novel technology reduces the size of the adipose tissue clusters by means of mild mechanical forces while eliminating pro-inflammatory oil and blood residue. The technique is gentle and provides micro-fragmented fat in a short time (15-20'), without expansion and/or enzymatic treatment. A 6 years old, mix breed, 24kg, dog, affected by mesothelioma was selected for the treatment. Autologous MFAT, obtained by lipoaspirate from the dog's lumbar flanks, was loaded with Paclitaxel (PTX), an anti-cancer chemotherapy drug, by adding it at a concentration of 1mg/ml and stirring the mixture for 30 minutes before the use. The mixture was administered by ultrasound guided intrathoracic and intraabdominal injections. Results. The dog presented rapid improvement in terms of general conditions after each intracavitary administration. This effect last for an average period of 30-40 days. During 22 months, the dog underwent 17 treatments, (both intrathoracic and intraabdominal) with an average of a treatment every 38 days. After treatment with LPG-PTX no drug was detected in the blood at 30 minutes. At 2, 4 and 8 hours only minimal part was detected. No minor or major complications were registered. The patient was euthanized after 22 months due to worsening of his clinical conditions and underwent a complete post mortem exam. Conclusions. Our data suggest that localized delivery of MFAT obtained by LG device and uploaded by PTX, directly into the peritoneal and thoracic cavity is feasible and safe. To our knowledge this is the first time that mesothelioma is treated using such a procedure in a dog and should be considered as a novel therapeutic approach. Survival time of 22 months was longer than 2 to 13 months reported in various studies of treated dogs. Furthermore, the lack of systemic absorption and any complications after intraabdominal and intrathoracic administration, may suggest a possible role of LG-PTX in other species, including man. The study of spontaneous, naturally occurring tumor in dogs is a model that provides a valuable role in developing successful, innovative treatment regimens for translational medicine facilitating the transfer of knowledge from the “bench” to the “bedside”.
Citation Format: Offer Zeira, Erica Ghezzi, Letizia Pettinari, Valentina Re, Davide Lupi, Silvia Benali, Simone Borgonovo, Giulio Alessandri, Francesco Petrella, Rita Paroni, Michele Deicas, Carlo Tremolada, Mirco Ponzoni, Valentina Coccè, Augusto Pessina. Microfragmented adipose tissue drug delivery in dog's mesothelioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-233.