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 Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>