Drug Conjugates Such as Antibody Drug Conjugates (ADCs), Immunotoxins and Immunoliposomes Challenge Daily Clinical Practice.docVIP

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Drug Conjugates Such as Antibody Drug Conjugates (ADCs), Immunotoxins and Immunoliposomes Challenge Daily Clinical Practice.doc

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Drug Conjugates Such as Antibody Drug Conjugates (ADCs), Immunotoxins and Immunoliposomes Challenge Daily Clinical Practice

Int. J. Mol. Sci. 2012, 13, 16020-16045; doi:10.3390/ijms131216020 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review Drug Conjugates Such as Antibody Drug Conjugates (ADCs), Immunotoxins and Immunoliposomes Challenge Daily Clinical Practice Wolf-Dieter Janthur, Nathan Cantoni and Christoph Mamot * Division of Hematology/Oncology, Cantonal Hospital of Aarau, CH-5001 Aarau, Switzerland; E-Mails: wolf-dieter.janthur@ksa.ch (W.-D.J.); nathan.cantoni@ksa.ch (N.C.) * Author to whom correspondence should be addressed; E-Mail: christoph.mamot@ksa.ch; Tel.: +41-62-838-6053; Fax: +41-62-838-6052. Received: 17 September 2012; in revised form: 15 November 2012 / Accepted: 19 November 2012/ Published: 28 November 2012 Abstract: Drug conjugates have been studied extensively in preclinical in vitro and in vivo models but to date only a few compounds have progressed to the clinical setting. This situation is now changing with the publication of studies demonstrating a significant impact on clinical practice and highlighting the potential of this new class of targeted therapies. This review summarizes the pharmacological and molecular background of the main drug conjugation systems, namely antibody drug conjugates (ADCs), immunotoxins and immunoliposomes. All these compounds combine the specific targeting moiety of an antibody or similar construct with the efficacy of a toxic drug. The aim of this strategy is to target tumor cells specifically while sparing normal tissue, thus resulting in high efficacy and low toxicity. Recently, several strategies have been investigated in phase I clinical trials and some have entered phase III clinical development. This review provides a detailed overview of various strategies and critically discusses the most relevant achievements. Examples of the most advanced compounds include T-DM1 and brentu