American Association for Cancer Research
15357163mct190826-sup-227986_3_supp_6169571_q7j9j9.docx (24.63 kB)

Table S2 from An Antibody–Drug Conjugate Targeting MUC1-Associated Carbohydrate CA6 Shows Promising Antitumor Activities

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journal contribution
posted on 2023-04-03, 18:22 authored by Céline Nicolazzi, Anne Caron, Alexia Tellier, Marc Trombe, Jan Pinkas, Gillian Payne, Chantal Carrez, Stéphane Guérif, Marie Maguin, Raffaele Baffa, Matteo Fassan, Julien Adam, Lydie Mangatal-Wade, Véronique Blanc

IHC detection in normal human tissues of MUC1 glycoprotein and CA6 glycotope


Immunogen and East Carolina University for their contribution

Thomas Jefferson University, Philadelphia, PA



Glycosylation is a complex multienzyme-related process that is frequently deregulated in cancer. Aberrant glycosylation can lead to the generation of novel tumor surface–specific glycotopes that can be targeted by antibodies. Murine DS6 mAb (muDS6) was generated from serous ovary adenocarcinoma immunization. It recognizes CA6, a Mucin-1 (MUC1)-associated sialoglycotope that is highly detected in breast, ovarian, lung, and bladder carcinomas. SAR566658 antibody–drug conjugate (ADC) is a humanized DS6 (huDS6) antibody conjugated through a cleavable linker to the cytotoxic maytansinoid derivative drug, DM4. SAR566658 binds to tumor cells with subnanomolar affinity, allowing good ADC internalization and intracellular delivery of DM4, resulting in tumor cell death (IC50 from 1 to 7.3 nmol/L). SAR566658 showed in vivo antitumor efficacy against CA6-positive human pancreas, cervix, bladder, and ovary tumor xenografts and against three breast patient-derived xenografts. Tumor regression was observed in all tumor models with minimal effective dose correlating with CA6 expression. SAR566658 displayed better efficacy than standard-of-care nontargeted tubulin binders. These data support the development of SAR566658 in patients with CA6-expressing tumors.