Resumen:
Canine mammary carcinomas (CMC) are associated with major aggressive clinical
behavior and high mortality. The current standard of care is based on surgical
resection, without an established effective treatment scheme, highlighting the
urgent need to develop novel effective therapies. Vascular endothelial growth
factor (VEGF) is a key regulator of tumor angiogenesis and progression in the
majority of solid cancers, including human and canine mammary carcinomas. The
first therapy developed to target VEGF was bevacizumab, a recombinant humanized
monoclonal antibody, which has already been approved as an anticancer agent in
several human cancers. The goal of this work was to establish the therapeutic
value of MB02 bevacizumab biosimilar in CMC. First, through different in silico
approaches using the MUSCLE multiple-sequence alignment tool and the FoldX
protein design algorithm, we were able to predict that canine VEGF is recognized
by bevacizumab, after showing an extremely high sequence similarity between
canine and human VEGF. Further, by using an ELISA-based in vitro binding assay,
we confirmed that MB02 biosimilar was able to recognize canine VEGF.
Additionally, canine VEGF-induced microvascular endothelial cell proliferation
was inhibited in a concentration-dependent manner by MB02 biosimilar. These
encouraging results show a high potential for MB02 as a promising therapeutic
agent for the management of CMC.
