Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen. - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue OncoImmunology Année : 2016

Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen.

Résumé

Antibody-drug conjugates (ADC), combining the specificity of tumor recognition by monoclonal antibodies (mAb) and the powerful cytotoxicity of anticancer drugs, are currently under growing interest and development. Here, we studied the potential of Chi-Tn, a mAb directed to a glyco-peptidic tumor-associated antigen, to be used as an ADC for cancer treatment. First, we demonstrated that Chi-Tn specifically targeted tumor cells in vivo. Also, using flow cytometry and deconvolution microscopy, we showed that the Chi-Tn mAb is rapidly internalized - condition necessary to ensure the delivery of conjugated cytotoxic drugs in an active form, and targeted to early and recycling endosomes. When conjugated to saporin (SAP) or to auristatin F, the Chi-Tn ADC exhibited effective cytotoxicity to Tn-positive tumor cells in vitro, which correlated with the level of tumoral Tn expression. Furthermore, the Chi-Tn mAb conjugated to auristatin F also exhibited efficient antitumor activity in vivo, validating for the first time the use of an anti-Tn antibody as an effective ADC.

Dates et versions

pasteur-01501030 , version 1 (03-04-2017)

Identifiants

Citer

Christine Sedlik, Adèle Heitzmann, Sophie Viel, Rafik Ait Sarkouh, Cornélie Batisse, et al.. Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen.. OncoImmunology, 2016, 5 (7), pp.e1171434. ⟨10.1080/2162402X.2016.1171434⟩. ⟨pasteur-01501030⟩
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