Adcitmer (R), a new CD56-targeting MMAE-conjugated antibody is a potential therapeutic approach in Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive skin cancer. While immune checkpoint inhibitors constitute a major advance for treating MCC patients with advanced disease, new therapeutic options are still urgently required. The aim of this study was to produce and evaluate therapeutic performances of a new Antibody-Drug Conjugate (ADC) targeting CD56, named Adcitmer®, in preclinical models of MCC. First, CD56 expression was evaluated in a MCC cohort (immunohistochemistry on tissue micro-array including 90 tumor samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56-positive MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. The Adcitmer® product was generated by bioconjugation of the CD56-targeting antibody to a cytotoxic anti-mitotic drug (MMAE) using McSAF® Inside bioconjugation process. Chemical properties and homogeneity of Adcitmer® were characterized by size-exclusion chromatography and mass spectrometry. Adcitmer® cytotoxicity was evaluated in vitro and in a xenograft mice model. CD56 was expressed by 66% of MCC tumors, confirming its relevance as therapeutic target. Specific binding and internalization of the unconjugated CD56-targeting antibody was validated in MCC cell lines. The high homogeneity of the newly generated CD56-targeting MMAE-conjugated antibody (Adcitmer®) was confirmed by size-exclusion chromatography. CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Adcitmer® significantly reduced tumor growth in a MCC mouse model. Our study suggests Adcitmer® as a therapeutic option to be further assessed in MCC patients, as an alternative or combined with immune checkpoint inhibitors.