Minnesota researchers refine experimental hemangiosarcoma treatment

Researchers at the University of Minnesota (UMN) College of Veterinary Medicine may be close to developing a genetically engineered treatment for dogs with hemangiosarcoma.

The experimental therapy combines a blood test that detects hemangiosarcoma cells with eBAT, which stands for epidermal growth factor (EGF) bispecific ligand-targeted angiotoxin.

An estimated 50,000 canine hemangiosarcoma cases are diagnosed each year in the U.S., according to Minnesota's veterinary researchers.

"Unfortunately, this disease is invariably fatal. More than 50% of dogs with this disease will die within four to six months, and almost 90% will die within a year. Surgery and chemotherapy can prolong life for dogs with hemangiosarcoma, but currently there is no cure," the site states.

Created by UMN medical oncologist Daniel Vallera, PhD, and refined by Dr. Jaime Modiano, director of UMN veterinary college's Animal Cancer Care and Research Program, eBAT fuses two antibody fragments, one for the EGF receptor and the other for the urokinase plasminogen-activator receptor, into an inactivated Pseudomonas exotoxin.

Because healthy cells almost never display both receptors, but hemangiosarcoma cells almost always do, eBAT enters malignant tissue, halts protein synthesis, and simultaneously destroys the endothelial cells feeding the tumor.

In a 2017 pilot study, 23 dogs received three eBAT infusions after splenectomy, but before standard doxorubicin chemotherapy. The six-month survival rate of the treated dogs improved to roughly 70%, and five dogs lived past 450 days.

Dr. Modiano called the outcome "the most significant advance in 30 years" for hemangiosarcoma, according to the American Kennel Club's Canine Health Foundation, a cosponsor of the study.

A follow-up study in 2020 pushed the dose to three full cycles in 25 dogs and narrowed the gap between when the toxin and chemotherapy were administered. However, the cancer persisted with six dogs experiencing significant hypotension. Additionally, the high survival rate disappeared.

"Our results indicate that repeated dosing cycles of eBAT starting 1 week prior to doxorubicin chemotherapy led to greater toxicity and reduced efficacy compared with a single cycle given between surgery and a delayed start of chemotherapy," the investigators concluded.

Dr. Modiano's research team is now investigating whether the blood test-eBAT combination can be used as a screening tool to predict the risk of dogs developing hemangiosarcoma or other life-threatening cancers and use such information to determine the best treatment options that may prevent or delay the onset of cancer.