Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Second Generation Targeted Antibodies - It’s All in the Binding

06.05.2004


The overproduction, or ‘overexpression’, of the epidermal growth factor receptor (EGFR) is one of the most common aberrations in cancer, and subsequently agents that inhibit EGFR are among the most hotly-pursued potential products in the pharmaceutical industry. Now, just weeks after one of the first anti-EGFR antibodies, ImClone’s Erbitux (Cetuximab), was approved for use in Europe and the USA, a ‘second generation’ anti-EGFR antibody is set to enter early-phase clinical trials in Australia. In two articles recently published in the Journal of Biological Chemistry, research teams from the Melbourne Branch of the international Ludwig Institute for Cancer Research (LICR) have elucidated the unique binding properties of an anti-EGFR antibody, called 806, that is able to discriminate between EGFR molecules on cancer cells and EGFR molecules on normal cells.



“There is already one anti-EGFR antibody on the market, and there are several more in clinical trials,” says Dr. Andrew Scott, the Head of the LICR Melbourne Branch’s Clinical Program. “Although these anti-EGFR antibodies do show some anti-tumor activity in patients, they are far from ideal because they bind to EGFR on both cancer cells and normal cells. As a result, they target normal tissues as well as the tumor, and side-effects, although mild, are common.” Perhaps more importantly, the ‘first generation’ antibodies are limited in their clinical application and their capacity for improvement. “We need to increase the therapeutic efficacy of the available anti-EGFR antibodies,” explains Dr. Scott. “What we would like to do is attach a lethal agent to an anti-EGFR antibody, such as a cytotoxic molecule or a radioisotope, so that the agent is targeted directly to the cancer cell. With the 806 antibody, we should be able to both interfere with EGFR signaling and deliver lethal agents to cancers, without causing severe side-effects through the destruction of normal, healthy cells, particularly in the liver and skin.”

The 806 antibody was originally discovered at the LICR’s New York Branch and has since been developed further through a concerted, international effort by LICR scientists at Branches in New York, San Diego, Stockholm, and Melbourne. The antibody was initially intended to target a mutated form of EGFR and was being developed as a treatment for brain tumors called glioblastomas. However, during comprehensive pre-clinical analyses it was found that the 806 antibody bound not only to the glioblastoma-specific mutant form of EGFR, it also bound to a significant proportion of EGFR positive cancers, but not to any normal tissue. The LICR teams subsequently showed that 806 has a potent anti-tumor activity in animal models of human cancers that overexpress EGFR.


The LICR Melbourne Branch has a longstanding research program in EGFR structure and biology, and in a recent pivotal discovery participated in defining the 3D-structures of the extracellular domains of the EGFR and a related protein, erbB2/HER-2, which is implicated in many breast cancers. The most recent papers describe in detail how EGFR undergoes alterations in its conformation as it is activated, and where the 806 antibody binds to the activated EGFR when the molecule is overexpressed on the surface of a cancer cell. According to Dr. Antony Burgess, the Director of the LICR Melbourne Branch, the elucidation of these conformational changes is crucial to designing more effective cancer therapies. “To rationally design antibodies that improve the targeting to EGFR, or any other cell surface receptor for that matter, you need to have an understanding of how the molecule works. The results from these two papers suggest how we might be able to design more antibodies, like 806, which bind to different conformations of a single molecule, and are thus able to discriminate between normal and tumor cells.”

Clinical-grade 806 antibody has been produced within LICR’s own biological production facilities for the first early-phase clinical trial. The trial, which will investigate the safety, dose, and tissue distribution of the 806 antibody in patients with head and neck or lung cancers, will commence in Melbourne this year.

Sarah White | LICR
Further information:
http://www.licr.org/C_news/040506_EGFR.php

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>