Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen. (2nd July 2016)

• Record Type: Journal Article
• Authors: Sedlik, Christine; Heitzmann, Adèle; Viel, Sophie; Ait Sarkouh, Rafik; Batisse, Cornélie; Schmidt, Frédéric; De La Rochere, Philippe; Amzallag, Nathalie; Osinaga, Eduardo; Oppezzo, Pablo; Pritsch, Otto; Sastre-Garau, Xavier; Hubert, Pascale; Amigorena, Sebastian; Piaggio, Eliane
• Is Part Of: Oncoimmunology. Volume 5:Number 7(2016)
• Publication Date: 2016-07-02
• Subjects: Biodistribution -- internalization -- MMAF -- monoclonal antibody-drug conjugate -- Tn antigen; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1171434
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.