Adcitmer ® , a new CD56‐targeting monomethyl auristatin E‐conjugated antibody, is a potential therapeutic approach in Merkel cell carcinoma

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Esnault, C. | Leblond, V. | Martin, C. | Desgranges, A. | Baltus, C.B. | Aubrey, Nicolas | Lakhrif, Z. | Lajoie, L. | Lantier, Louis | Clémenceau, B. | Sarma, B. | Schrama, J. | Houben, R. | Schrama, D. | Hesbacher, S. | Gouilleux-Gruart, Valérie | Feng, Y. | Dimitrov, D. | Guyétant, Serge | Berthon, Patricia | Viaud‐massuard, M.C. | Samimi, Mahtab | Touzé, Antoine | Kervarrec, T.

Edité par CCSD ; Wiley -

International audience. 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® ) 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® product was generated by the bioconjugation of CD56-targeting antibody to a cytotoxic drug (monomethyl auristatin E) using the McSAF Inside® bioconjugation process. The 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 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® was confirmed by hydrophobic interaction chromatography. The CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer® significantly reduced tumour growth in a MCC mouse model.Conclusions: Our study suggests that Adcitmer® 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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