Background
Endothelin 1 receptors are one of the drivers of tumor progression in many cancers. Inhibition of their signaling pathways with antagonist drugs has been the subject of numerous clinical trials, but the
Conclusions
xiRB49-MMAE is a promising drug candidate for clinical trials in ETB+ tumors. RB49 could be used as a diagnostic tool for patient stratification.
Methods
We previously reported the rendomab B49 antibody (RB49) exhibiting a preferential affinity for the activated conformation of human endothelin B receptor (ETB), not displaced by high endothelin levels, and without any pharmacological properties that could inhibit the division of melanoma cells. In this context, we have developed xiRB49-MMAE, a chimeric antibody-drug conjugated (ADC) to monomethyl auristatin E. We have characterized its physicochemical properties, studied its binding mechanisms, and evaluated its therapeutic potential in a preclinical model. Immunohistochemical analysis of metastatic melanoma lymph nodes evaluated RB49 as a diagnostic tool for patient stratification.
Results
xiRB49-MMAE showed high efficacy against melanoma cells and ETB+ xenograft tumor models. IHC studies indicated that 100% of melanoma patient lymph node biopsies were RB49-positive. Conclusions: xiRB49-MMAE is a promising drug candidate for clinical trials in ETB+ tumors. RB49 could be used as a diagnostic tool for patient stratification.