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Web End = Pharm Res (2015) 32:34513452 DOI 10.1007/s11095-015-1775-2
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Antibody-Drug Conjugates
Ashutosh A. Kulkarni1 & Hovhannes J. Gukasyan2
Received: 5 August 2015 /Accepted: 10 August 2015 /Published online: 15 August 2015 # Springer Science+Business Media New York 2015
Antibody-drug conjugates (ADCs) are an exciting and new class of therapeutic modalities that have gained significant traction over the past few years specifically in the field of oncology. With the recent approvals of CD-30 directed Adcetris (brentuximab vedotin) and the Her2 targeted Kadcyla (ado-trastuzumab emtansine) and hundreds of other ADCs in various stages of drug discovery and development, the field is experiencing significant optimism and interest from the biopharmaceutical industry. Several esteemed organizations including Celgene, Immunogen, Pfizer, Agensys, and Genentech to name a few are investing significant resources into ADC discovery and development. The lure of ADCs is that they combine the specificity of a monoclonal antibody with the potent cytotoxicity of a small molecule toxin payload. The hypothesis is that by combining these 2 characteristics, one should be able to specifically target the ADC to the diseased tissue and steer clear of the non-specific toxicity of the toxin payload. Also, the presence of the toxin payload would make the ADC significantly more efficacious compared to antibody alone. One of the key benefits is that the antibody does not necessarily need to have therapeutic activity on its own since the efficacy of ADC is driven by internalization of the ADC moleculetrafficking to the lyso-somedegradation to the final catabolitecytotoxic activity of the catabolite on the cellular machinery.
However,...