Grigory Ryzhakov – Russian Writer

Taking Lives, Getting Antibodies – Subject to change

How do we save a rabbit?

Antibodies are proteins produced in animals as a part of the immune response. Thousands of laboratories around the world use antibodies to detect biological macromolecules. Some great drugs, like anticancer medicines or vaccines, are, in fact, antibodies.

The popularity of antibodies in experimental biology is based on the affinity (tightness of binding) and specificity of their target recognition. You can raise an antibody, which would recognize one unique region of the molecule, this region is also scientifically called antigen, in cells containing millions of potential antigens. So, antibodies are like keys to locks. Each key is unique. Our organism is able to produce virtually any kind of these keys to any kind of locks. Amazing!

But that is in theory. In practice, majority of the commercially available antibodies, quite costly, perform badly or don’t work at all. It means their affinity and specificity aren’t up to scratch.

Another bad thing is that one needs to sacrifice animals, like rabbits or goats, to raise antibodies, which is quite wasteful especially if many antibodies turn out to be useless.

But there is an alternative. Thankfully we live in a post-genomic era and we can actually design any antibodies synthetically without any animal use. The technology is called phage display, it is based on use of bacterial viruses (called bacteriophages). There are related technologies now (like mRNA or ribosome displays), but I’ll carry on with this one, because it’s used the most.

It works well (I won’t bore you with technicalities) and there are already some companies out there providing their services in producing phage antibodies. Some why the vast majority of scientists, including me, are still using the conventional antibodies from animals? I think it’s an old habit. Even in science a progress can be slow and some technologies take awhile to kick in. And, you don’t have to wait for an antibody being produced (it takes 3-4 weeks to generate an antibody response in a rabbit), since for a majority of known proteins there are ready-made antibodies available.

But I guess the major reason is money. A vial of the commercially available antibody costs $200-300, while generating phage antibody clones would currently cost you $7000-10000. So you pay a lot less and get limited amounts and likely poor performance, while you’d want unlimited supply and top quality. But you have no money. What is to be done? The answer is “Make yours!”

Imagine that you are an average, rather poor, scientist and you need a hundred of different antibodies for your experiment. How much do you think it would cost you to produce them? And how many animals would you need to sacrifice? Yes, the phage display system costs something to get in place, but it is totally worth it in the long run. Think about how many new discoveries you can make by using high affinity and specificity antibodies. Here is the success story.

I’ve recently attended a talk by John McCafferty, one the pioneers who started making antibodies using phage display. He was also a co-founder of Cambridge Antibody Technology (CAT). One of the first commercially successful antibodies CAT generated was HUMIRA, a phage antibody recognizing an important human immune factor called TNF-alpha. In many autoimmune conditions such as rheumatoid arthritis overproduction of TNF-alpha correlates with the severity of disease. HUMIRA binds TNF-alpha and blocks its autoimmune properties. This antibody is now being used in the clinic to treat arthritis; the annual sales of HUMIRA exceed $1 billion.

Currently John runs a lab at Cambridge: he uses the technology to study cell-to-cell communication.  Scientists are more likely to trust the data from his lab, because he uses high-affinity and specificity phage antibodies.

And I believe that to do top science one requires quality methods and reagents.

So, is antibody production by phage display a technology with enormous potential? Will it soon become more common and cheaper to use? I don’t know, but I’m all for it.

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