Human monoclonal antibody fragments targeting matrilin-3 in growth plate cartilage
Pharmaceutical research, 2015•Springer
Purpose Many genetic disorders, including chondrodysplasias, and acquired disorders
impair growth plate function, resulting in short and sometimes malformed bones. There are
multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate,
which could potentially be used to treat these disorders. Targeting these growth factors
specifically to the growth plate might augment the therapeutic skeletal effect while
diminishing undesirable effects on non-target tissues. Methods Using yeast display …
impair growth plate function, resulting in short and sometimes malformed bones. There are
multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate,
which could potentially be used to treat these disorders. Targeting these growth factors
specifically to the growth plate might augment the therapeutic skeletal effect while
diminishing undesirable effects on non-target tissues. Methods Using yeast display …
Purpose
Many genetic disorders, including chondrodysplasias, and acquired disorders impair growth plate function, resulting in short and sometimes malformed bones. There are multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate, which could potentially be used to treat these disorders. Targeting these growth factors specifically to the growth plate might augment the therapeutic skeletal effect while diminishing undesirable effects on non-target tissues.
Methods
Using yeast display technology, we selected single-chain variable antibody fragments that bound to human and mouse matrilin-3, an extracellular matrix protein specifically expressed in cartilage tissue. The ability of the selected antibody fragments to bind matrilin-3 and to bind cartilage tissue in vitro and in vivo was assessed by ELISA and immunohistochemistry.
Results
We identified antibody fragments that bound matrilin-3 with high affinity and also bound with high tissue specificity to cartilage homogenates and to cartilage structures in mouse embryo sections. When injected intravenously in mice, the antibody fragments specifically homed to cartilage.
Conclusions
Yeast display successfully selected antibody fragments that are able to target cartilage tissue in vivo. Coupling these antibodies to chondrogenic endocrine and paracrine signaling molecules has the potential to open up new pharmacological approaches to treat childhood skeletal growth disorders.
Springer