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

Background Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumour cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating patients with MCC with advanced disease, new therapeutic options are still urgently required. Objectives To produce and evaluate the therapeutic performance of a new antibody-drug conjugate (Adcitmer(R)) targeting CD56 in preclinical models of MCC. Methods CD56 expression was evaluated in a MCC cohort (immunohistochemistry on a tissue microarray of 90 tumour samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56(+) MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. Adcitmer(R) product was generated by the bioconjugation of CD56-targeting antibody to a cytotoxic drug (monomethyl auristatin E) using the McSAF Inside(R) bioconjugation process. The chemical properties and homogeneity of Adcitmer(R) were characterized by hydrophobic interaction chromatography. Adcitmer(R) cytotoxicity was evaluated in vitro and in an MCC xenograft mice model. Results Similar to previous reports, CD56 was expressed by 66% of MCC tumours in our cohort, confirming its relevance as a 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(R) was confirmed by hydrophobic interaction chromatography. The CD56-mediated cytotoxicity of Adcitmer(R) was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer(R) significantly reduced tumour growth in a MCC mouse model. Conclusions Our study suggests that Adcitmer(R) should be further assessed as a therapeutic option in patients with MCC, as an alternative therapy or combined with immune checkpoint inhibitors.

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