Grant No. 1139: Immune Targeting of Canine Hemangiosarcoma Using a Canine Derived Single Chain Antibody Approach
Primary Investigator: Dr. Nicola Mason, PhD
Institution: University of Pennsylvania, School of Veterinary Medicine
Total Grant Amount: $123,125.40
Requested Sponsorship: $2,500
Project Abstract:
Canine hemangiosarcoma is a common and highly aggressive tumor of blood vessels that is oftentimes fatal. At diagnosis most dogs have evidence of metastatic disease and despite chemotherapy, survival times rarely exceed 6 months. Novel approaches to the treatment if this disease are needed. The use of monoclonal antibodies and antibody fragments to directly target different tumors has shown promise in clinical trials in man. It is the aim of this proposal to use a novel canine synthetic antibody system to specifically target the tumor and deliver cytotoxic agents directly to both primary and metastatic lesions. Using advanced molecular techniques, we intend to recapitulate antibody responses that dogs with hemangiosarcoma may make against their own tumors and use these as a template to generate canine antibody fragments that specifically recognize tumor particles. Tumor-specific antibody fragments will be linked to an exotoxin and evaluated for their ability to kill canine hemangiosarcoma cells in vitro. Immune-mediated targeting of tumors allows for the direct delivery of cytotoxic agents to the tumor, thus decreasing side effects and increasing therapeutic efficacy. This work aims to develop the first canine-derived, tumor-specific targeting approach for the treatment of HSA and to provide proof-of-principal for this approach that can then be used to therapeutically target many other tumor types in this species in vivo.