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.
Sarah White | LICR
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Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.
Graphene is up to the job
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
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