Linked-in: design and efficacy of antibody drug conjugates in oncology.

Abstract

The use of antibody drug conjugates (ADCs) as targeted chemotherapies has successfully entered clinical practice and holds great promise. ADCs consist of an antibody and toxin-drug combined together via a chemical linker. While the antibody and drug are of vital importance in the direct elimination of cancer cells, more advanced linker technology was instrumental in the delivery of more potent drugs with fewer side effects. Here, we discuss the preclinical experience as well as clinical trials, with a specific emphasis on the clinical outcomes and side effects, in addition to linker strategies for five different ADCs, in order to describe different approaches in the development of this new class of anticancer agents. Brentuximab vedotin is approved for use in Hodgkin's lymphoma and Trastuzumab emtansine is approved for breast cancer. Combotox, Inotuzumab Ozogamicin, and Moxetumomab Pasudotox are in various stages of clinical development and are showing significant efficacy in lymphoid malignancies. These ADCs illustrate the promise and future potential of targeted therapy for presently incurable malignancies.

• Authors: Jonathan Feld, Stefan K Barta, Carolina Schinke, Ira Braunschweig, Yiyu Zhou, Amit K Verma
• Journal: Oncotarget (Oncotarget) Vol. 4 Issue 3 Pg. 397-412 (Mar 2013) ISSN: 1949-2553 [Electronic] United States
• PMID: 23651630 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Immunoconjugates

Topics

• Antineoplastic Agents (chemistry, immunology, therapeutic use)
• Chemistry, Pharmaceutical (methods, trends)
• Clinical Trials as Topic
• Drug Design
• Humans
• Immunoconjugates (chemistry, immunology, therapeutic use)
• Models, Immunological
• Neoplasms (drug therapy, immunology, pathology)
• Treatment Outcome