WEAVE project “Common targetable biomarkers in canine hemangiosarcoma and human angiosarcoma”

Lead partner: UNG (Ario de Marco). Other partners: Dr. Hilde de Rooster (Ghent University, Belgium) and Dr. Antonio Cosma (Luxembourg Institute of Health)

Duration: Nov 2023 - Oct 2026

Topic:

The higher incidence of some malignancies in dogs can represent an invaluable option for studying rare pathologies in humans. Dogs represent an excellent translational model since they develop spontaneous tumors that share many clinical and epidemiologic features with human cancers, including histologic morphology, tumor genetics, molecular targets, biological behavior, and response to conventional therapies. In contrast to rodents bearing induced tumors that do not represent the structural and genetic complexity of spontaneous tumors, cancer in pet dogs develops naturally in the context of an intact immune system, which is characterized by tumor growth over long periods of time developing recurrence and metastasis to relevant distant sites.

Angiosarcoma (AS) is a rare (1 case/1 million people, corresponding to roughly 1% of all yearly diagnosed sarcomas), genomically complex and aggressive vascular sarcoma. The limited availability of patients impaired the development of effective therapies and consequently, the survival rate is dramatically poor. Dogs spontaneously develop histologically similar neoplasia, hemangiosarcoma (HSA), that is relatively common representing 5-7% of all canine malignant tumors with an incidence that is significantly higher in breeds such as German shepherd and boxer. Both AS and HSA are considered to originate from hematopoietic endothelial progenitor cells. Despite the fact that AS is predominantly cutaneous in humans and HSA is visceral in the vast majority of dogs, metastasis are mostly localized in lungs and liver in both models and comparative genomic analyses confirmed strong similarities between AS and HSA as well as the high but convergent heterogeneity within and between patients of both species. At protein level, immune histochemical analyses of canine samples indicated the overexpression of CD31, VEGFR1, VEGFR2, VEGFR3, PDGFRA/B, MUC18, c-Kit and FGFR1 in at least part of the evaluated specimens and consequently such receptors could serve as HSA membrane, accessible markers. Data relative to AS cell surface targetable biomarkers are more limited in number but suggest overexpression of VEGF receptors as well as of c-Kit. It would be particularly useful to identify further surface biomarkers shared by AS and HSA cells to develop targeting strategies suitable for both species. The HSA prevalence and the prior knowledge justifies the interest for exploring HSA as a tractable model for studying human AS, developing drug- and immunotherapies as well as for testing experimental therapies in clinical trials.

This project general aim is to isolate a set of immunoreagents suitable for the characterization, diagnostics and, potentially, therapy of (splenic) HSA in dogs. They should target biomarkers exposed at the cell surface, allowing the selective targeting of the corresponding cells in tissues. Furthermore, they could serve as reagents for implementing similar diagnostic protocols in human AS. However, information and reagent transfer between HSA and AS will only be suitable and reliable if the similarity between the two biological systems is sufficiently high. Consequently, the conservation of epitopes between HSA and AS cells needs to be first be evaluated and, for accomplishing this task, we’ll exploit the large pool of anti-HSA reagents that will be recovered by panning ligand libraries against the tumor biomarkers to obtain a multidimensional profile of both HSA and AS exposed proteomes. The achievement of these objectives will be obtained by means of a multidisciplinary, collaborative team involving the complementary expertise of UNG (nanobody technology) and of two strategic partners, Hilde de Rooster at Ghent University (veterinary oncology surgery) and Antonio Cosma at the Luxembourg Institute of Health (flow and mass cytometry).