Adcitmer® , a new CD56-targeting MMAE-conjugated antibody is a potential therapeutic approach in Merkel cell carcinoma.

Background Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumor cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating MCC patients with advanced disease, new therapeutic options are still urgently required. Objective The aim of this study was to produce and evaluate therapeutic performances of a new antibody-drug conjugate targeting CD56, named Adcitmer®, in preclinical models of MCC. Methods First, CD56 expression was evaluated in an 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. Adcitmer® product was generated by bioconjugation of CD56-targeting antibody to a cytotoxic drug (MMAE) using McSAF Inside® bioconjugation process. Chemical properties and homogeneity of Adcitmer® were characterized by hydrophobic interaction chromatography. Adcitmer® cytotoxicity was evaluated in vitro and in an MCC xenograft mice model. Results Similar to previous reports, CD56 was expressed by 66% of MCC tumors in our cohort, 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 Adcitmer® was confirmed by hydrophobic interaction chromatography. CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer® significantly reduced tumor growth in a MCC mouse model. Conclusion Our study suggests Adcitmer® as a therapeutic option to be further assessed in MCC patients, as an alternative or combined with immune checkpoint inhibitors.