2016 ACVIM Forum Research Abstract Program

ENHANCEMENT OF DOXORUBICIN EFFECTIVENESS WHEN COMBINED WITH SALINOMYCIN IN FISS CELL LINES. Lucia Borlle 1 , Brittany Zumbo 2 , Kelly R. Hume 1 . 1 Cornell University, Ithaca, NY, USA, 2 Michigan State University, MI, USA Feline injection site sarcoma (FISS) is an aggressive neoplasia that remains a challenge for clinicians. Radical surgery is the first choice treatment but is not always feasible. Chemotherapeutic responses have been documented but are generally of short duration; tumors often develop resistance quickly. Salinomycin is an ionophore that has been shown to inhibit cancer stem cells and to increase the sensitivity of human soft tissue sarcoma cells to doxorubicin chemotherapy. The aim of our study was to determine if salinomycin could be used to increase the sensitivity of FISS cell lines to doxorubicin. Two primary cell lines cultured from feline patients with histologically confirmed FISS were used for this purpose. Since the threshold response to doxorubicin differs, we ranked the cells according to the sensitivity to doxorubicin and used one sensitive line (C10) and one resistant line (B4). Cell viability assays (MTT) were used to determine the response to single agent and combination therapy. Three independent assays were performed, with samples evaluated in triplicate in each assay. Student's t-tests were employed to compare the results of individual doxorubicin concentrations with and without salinomycin combination therapy. Addition of 5 uM salinomycin resulted in a statistically significant (P < 0.05) reduction in cell viability compared to single agent doxorubicin at multiple concentrations for both cell lines. Our results highlight a potential chemotherapy protocol for the treatment of FISS. Further investigations need to be pursued to define the effect of this novel therapeutic combination and to validate our results in vivo. Canine Non-Hodgkin's lymphoma (NHL) occurs in approximately 30-100/100,000 dogs per year and accounts for up to 83% of canine hematopoietic cancers. Standard-of-care treatment for canine NHL comprises multi-drug chemotherapeutic protocols. 60-85% of dogs enter a complete clinical remission following induction chemotherapy, and median first-remission durations range from 140 to 385 days. Resistance to chemotherapy increases with each subsequent relapse and less than 10% of patients survive longer than 2 years from diagnosis. To prolong overall survival, more effective therapies are required to prevent relapse following successful induction chemotherapy. Directing the immune system to specifically target malignant cells is a powerful strategy in the treatment of cancer. We have previously developed a vaccine strategy that utilizes autologous CD40-activated B cells as antigen-presenting cells electroporated with autologous tumor RNA as the antigenic payload to stimulate anti-tumor immunity in dogs with NHL. In our first clinical trial, we showed that dogs vaccinated three times at three week intervals following successful induction chemotherapy had a tendency towards prolonged remission times and overall survival when compared to historical controls. Furthermore, vaccinated dogs that did relapse showed a statistically significant increase in overall survival following rescue chemotherapy. These results coupled with immune analysis from vaccinated patients suggested that while RNA loaded CD40-activated B cells primed an anti-tumor immune response, it was insufficient to maintain remission. Fur