Code Name: Pentabody

Gloved hand representing the role of a Pentabody

Canadian biotechnology companies and researchers were out in force at the recent BIO 2005 International Convention in Philadelphia. With 18,000 attendees overall, the conference is arguably the signature event in this high-growth, value-added industry. 

Dr. Yves Geoffrion, member of the business development team at Ottawa's NRC Institute for Biological Sciences (NRC-IBS) was there to scope out the opportunities – and the competition! – that a start-up Canadian company might find when moving forward in commercializing a NRC technology involving the artificial production of antibodies.

Code-named 'Pentabody', this NRC-IBS technique for the rapid production of custom antibodies is on the commercialization path. The technology's commercial potential recently impressed a panel of distinguished business and science leaders to the extent that they awarded it the top prize in the 2005 edition of NRC's Business Case Challenge. The Pentabody technology will be the subject of a milestones-dependent license to Qbiotyx, an Ottawa-based "spin-in" development company led by David Smith, who brings more than 20-years of international experience and contacts in the diagnostics industry.

How do antibodies work?

An antibody is a natural type of protein produced by white blood cells when mounting an immune response to a foreign substance (an antigen) introduced in the body. The antibody latches onto the antigen and either destroys it directly or makes it easier for white blood cells to do the job.

Diagram of the molecular representation of the Pentabody, where each 'finger' is an antibody monomer

For more than 25 years, following the seminal research on monoclonal antibodies that led to a Nobel prize, scientists have taken advantage of the complex and labour-intensive process of producing antibodies in the laboratory. This has become the workhorse of the biotechnology laboratory and has led to highly effective diagnostic tests for everything from pregnancy, heart attack or cancer detection.

But, the current generation of antibody-based diagnostic tools are difficult and costly to produce. And, in some cases, the large antibody molecule simply has a hard time grabbing and holding on to its target, similar to trying to grasp something with one finger when a hand, with five fingers, would be better. In contrast, the Pentabody provides such a customized molecular handle for a given target.

That's because of the Pentabody's molecular shape, resembling a starfish - or a hand! - with each one of the five identical "fingers" being a small, man-made, antibody.

"In terms of efficacy, this increases the Pentabody's affinity for its target not by five, but by as much as 10,000 times," says Dr. Roger MacKenzie, a veteran NRC-IBS scientist and co-inventor of the Pentabody technology.

Not only are pentabodies a step-up when it comes to binding their target antigen, they also represent a five-fold increase in the speed with which antibodies can be obtained.

"The bottleneck of current antibody production methods is the inability to obtain, rapidly and consistently, well-defined antibodies based on customer specifications," says Dr. Geoffrion, the point business person for the Pentabody technology at NRC-IBS.

The Pentabody team believes their technology has what it takes to overcome this bottleneck.

Rather than using an animal to produce the initial antibodies, the Pentabody system is based on a well-established process to rapidly isolate antibodies from an antibody "library" contained in a test-tube. The antigen (a protein, toxin or other target molecule) is added to this mix of tens of millions of potential antibodies, and in a selection process based on molecular affinity, the antigen and its antibody bind to one another. Using bioengineering techniques, the singled-out (monomer) antibodies are then replicated en masse.

The next step is the critical one in creating the Pentabody. The selected monomer antibody is engineered to fit into a star-shaped protein . These components are then formulated into a Pentabody, with its five arms – or fingers! – each incorporating the selected monomer antibody.

"With this technique we can have a patent protected Pentabody produced within 21 working days," says Dr. Jianbing Zhang, a NRC-IBS scientist and co-inventor of the Pentabody technology.

If all goes according to plan, following a diligent intellectual property review this year Qbiotyx will propose contract Pentabody production to the market served by current monoclonal antibody producers. This includes in-vitro diagnostic kit manufacturers, pharmaceutical companies that use antibodies for detecting drug candidates, and academic researchers.

However, in the long term the Pentabody team believes their "five-fingered" technology is capable of offering a firm grip on the rapidly growing and changing antibody market, with new antibody applications including cancer therapies and diagnostic imaging.

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