The invention relates to two isolated human neutralizing antibodies that binds to an undisclosed Tyrosine Kinase Receptor, which further induces internalization and degradation of oncogenic forms of this Receptor.
The invention is based on the generation and characterization of two neutralizing scFv-Fc which interfered with ligand binding and consequently, inhibited ligand-dependant Tyrosine Kinase Receptor phosphorylation and downstream signalling.
These antibodies reduced the viability of erythroleukemic cell line UT-7, after 3 days of treatment. These anti-TK Receptor scFv-Fc also reduced cell viability of two mast cell leukemia cell lines bearing activating mutations of the TK Receptor.
Inhibition was due to intensive internalization and degradation of oncogenic forms of the TK Receptor upon antibody treatment.
These fully human antibodies thus represent new therapeutic tools useful for targeting diseases associated with Receptor or Ligand overexpression as well as for targeting oncogenic TK Receptor signalling in cancer such as AML or GIST, and to bypass Tyrosine Kinase Inhibition resistance of certain mutants.