Toceranib phosphate

Cell experiment:

The c-kit mutant canine C2 mastocytoma cell line, derived from a spontaneously occurring cutaneous mast cell tumors (MCTs), is used as the parental cell line. Cells are propagated in RPMI 1640 supplemented with 2 mM L-glutamine, 10% FBS, 100 g/mL Streptomycin, and 100 U/mL Penicillin in a 37°C incubator under a humidified atmosphere of 5% CO2. Toceranib-resistant C2 cells are selected by growing C2 cells in concentrations of Toceranib ranging from 0.02 uM to 0.3 uM and increasing in 0.025-0.05 uM increments. Three independent, Toceranib -resistant sublines are established over a period of 7 months[2].

Animal experiment:

Dogs[3]Fifteen client-owned dogs with advanced tumors are used. Dogs receive Toceranib at 2.75 mg/kg once every other day. After 2 weeks, oral cyclophosphamide (CYC) is added at 15 mg/m2 daily. Numbers of Treg and lymphocyte subsets are measured in blood by flow cytometry during the 8-week study period. Serum concentrations of IFN-γ are measured by ELISA.

References:

[1]. London CA, et al. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res. 2003 Jul;9(7):2755-68.
[2]. Halsey CH, et al. Development of an in vitro model of acquired resistance to toceranib phosphate (Palladia ) in canine mast cell tumor. BMC Vet Res. 2014 May 6;10:105.
[3]. Mitchell L, et al. Clinical and immunomodulatory effects of toceranib combined with low-dose cyclophosphamide in dogs with cancer. J Vet Intern Med. 2012 Mar-Apr;26(2):355-62.