Chemically Defined Antibody– and Small Molecule–Drug Conjugates for in Vivo Tumor Targeting Applications: A Comparative Analysis

• Published in: Journal of the American Chemical Society Vol. 140; no. 5; pp. 1617 - 1621
• Main Authors: Cazzamalli, Samuele, Dal Corso, Alberto, Widmayer, Fontaine, Neri, Dario
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.02.2018
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Antigens, Neoplasm - metabolism; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrase IX - antagonists & inhibitors; Carbonic Anhydrase IX - metabolism; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Humans; Kidney Neoplasms - drug therapy; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Tumor Hypoxia - drug effects
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.7b13361

We present the first direct comparative evaluation of an antibody–drug conjugate and of a small molecule–drug conjugate for cancer therapy, using chemically defined products which bind with high-affinity to carbonic anhydrase IX, a marker of tumor hypoxia and of renal cell carcinoma.