Adcitmer®, a new CD56‐targeting monomethyl auristatin E‐conjugated antibody, is a potential therapeutic approach in Merkel cell carcinoma. (1st February 2022)

• Record Type: Journal Article
• Authors: Esnault, C.; Leblond, V.; Martin, C.; Desgranges, A.; Baltus, C.B.; Aubrey, N.; Lakhrif, Z.; Lajoie, L.; Lantier, L.; Clémenceau, B.; Sarma, B.; Schrama, J.; Houben, R.; Schrama, D.; Hesbacher, S.; Gouilleux‐Gruart, V.; Feng, Y.; Dimitrov, D.; Guyétant, S.; Berthon, P.; Viaud‐Massuard, M.C.; Samimi, M.; Touzé, A.; Kervarrec, T.
• Is Part Of: British journal of dermatology. Volume 186:Number 2(2022)
• Page Start: 295
• Page End: 306
• Publication Date: 2022-02-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.20770
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: 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.