Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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


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:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

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: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>