spacer
home > ebr > spring 2007 > antibody conjugates promise to deliver
PUBLICATIONS
European Biopharmaceutical Review

Antibody Conjugates Promise to Deliver

Shane Olwill, Richard Buick and Christopher Scott at Fusion Antibodies examine emerging strategies for the application of antibody conjugates therapeutics

Antibodies represent the single most exciting drug class currently under clinical development. However, they are also effective agents for site specific delivery of other therapeutic agents within the body. With optimised synthesis and formulation, this approach frequently results in the generation of therapeutically useful levels of drug which have been unattainable at the site of disease through more conventional pharmaceutical delivery approaches. This short review looks at antibody conjugates that are currently in the clinic, and the main strategies being examined for the development of new therapeutic antibody conjugates.

WHY USE ANTIBODY DRUG CONJUGATES?

The application of antibody-based products in the pharmaceutical industry is well established, with over 20 antibody-based products currently marketed for the treatment of conditions including cancer, viral and inflammatory diseases. Sales from this class of therapeutic reached $2 billion in 2000 and are expected to grow to over $25 billion by 2010. It is with little surprise, therefore, that they represent the fastest growing class of drug currently in clinical development.

These biopharmaceuticals elicit their therapeutic effect by docking to a specific binding site or epitope, normally on a targeted protein at the site of disease, leading to a direct or indirect biological response. The selective ability of the antibody to localise to the targeted protein is key to success; large R&D investments across the private and public biotechnology sectors have been dedicated to the identification of suitable unique targets or biomarkers in various disease models. Historically, biomarkers have been examined for the ability of the antibody binding to elicit a desired therapeutic response. For example, trastuzumab (Herceptin) is used in the treatment of early breast cancer where it binds to the cell surface protein HER2/neu, inhibiting proliferation pathways that transduce through this signalling receptor, thus attenuating the growth of the tumour. Alternatively, bevacizumab (Avastin) inhibits the formation of new blood vessels (angiogenesis) in colorectal tumours by sequestering and removing the major proangiogenic factor vascular endothelial growth factor (VEGF) from the tumour micro-environment.

In addition to the active docking of the antibody to its cognate target, it is thought that the antibodies can also elicit their effect on diseased cells by virtue of their constant fragment (Fc)region. There are two possible mechanisms: antibodydependent cellular cytotoxicity (ADCC) and complementdependent cytotoxicity (CDC). In ADCC, the antibody binds to the surface of the diseased cell and the presence and surface density of their Fc regions leads to recruitment of immune effector cells (1). It is thought that trastuzumab is able to increase its effects against HER2/neu breast cancer cells by evoking this response. Alternatively, CDC refers to the recruitment and activation of the complement system by the antibody (2), and is thought to play a role in the therapeutic effect of the anti-CD20 antibody rituximab, used in the treatment of Non-Hodgkin’s lymphoma.


Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer

Shane Olwill is the Director of Research and Development at Fusion Antibodies Ltd, a Belfast-based biotechnology company specialising in the development of antibody-based therapeutics in the areas of oncology and angiogenesis. He gained his PhD from the University of Ulster, where he researched alterations in molecular pharmacology as a result of leukemia chemotherapy. Prior to joining Fusion Antibodies, Shane worked in several public and private sector medical laboratories.

Richard Buick is Technical Director of Fusion Antibodies Ltd, prior to which he spent four years at Randox Laboratories as a leader of the molecular biology and protein expression team. Richard has a PhD in Recombinant Antibody Engineering Technologies from the Centre for Cancer Research and Cell Biology, Queen’s University, Belfast, and leads antibody engineering research at Fusion Antibodies.

Christopher Scott is a Lecturer in Biomolecular Science at the School of Pharmacy, Queen’s University, Belfast, UK. He has broad expertise in a wide range of protein expression and capture methodologies, has a PhD in Protease Biochemistry, and was an original member of the founder research team at Fusion Antibodies Ltd. In 2003, Chris joined Queen’s to establish his research team focusing on the development of novel antibodybased therapeutic strategies for the treatment of cancer.

spacer
Shane Olwill
spacer
spacer
spacer
Richard Buick
spacer
spacer
spacer
Christopher Scott
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

MedPharm’s CSO and University of Reading Professor co-author new book on dermal formulation development

MedPharm’s Chief Scientific Officer and Co-Founder, Professor Marc Brown and University of Reading’s Professor Adrian Williams have co-authored the new book: ‘The Art and Science of Dermal Formulation Development”. It is the latest addition to ‘Drugs and the Pharmaceutical Sciences’, a series of textbooks and monographs published by CRC Press.
More info >>

White Papers

Challenges of Analytical Method Transfer in the Pharmaceutical Industry

RSSL

The development and validation of suitable analytical methods is a critical part of the overall drug-development life-cycle. For the majority of products, particularly those that are clinically successful, the transfer of the analytical method between laboratories will be required. This process is designed to verify that a given laboratory is capable of performing a test method for its intended purpose. This can be performed either internally (at the same company), or, with the on-going increasing trend in outsourcing, to an external Contract Research or Development organisation (CRO or CDO).
More info >>

 
Industry Events

CPhI & P-MEC China

18-20 June 2019, SNIEC, Shanghai, China

CPhI & P-MEC China 2019 is your gateway to successfully grow your business at the 2nd largest pharma market in the world. Whether you are looking for sourcing new business or getting the latest market insight, this is your one-stop shop pharmaceutical platform in Asia.
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement