Fishing for cancer cures: our new Cancer Research UK-MedImmune Alliance Laboratory

A droplet of clear liquid in a plastic tube no bigger than a Biro lid may not look that impressive, but it could hold the cancer cures of the future.

This precious fluid isn’t merely water. It’s teeming with billions of microscopic viruses, each producing a unique antibody (a special type of protein normally produced by our immune cells).

Drugs based on antibodies, such as Herceptin and rituximab, have transformed survival for breast and blood cancers respectively, and antibodies also lie at the heart of the new generation of immunotherapy drugs that we’ve heard so much about recently.

Many more potentially life-saving therapies are trapped inside a tiny tube like this – all we need to do is fish them out.

And in order to do so, we’ve set up an exciting new lab in partnership with the Cambridge-based research company MedImmune.

Antibodies on display

The newly-opened Cancer Research UK MedImmune (CRUK-MEDI) Alliance Laboratory will specialise in a type of technology called phage display, allowing researchers to quickly scan through millions upon millions of randomly-generated antibodies to find ones that recognise important molecules involved in cancer or other diseases.

First developed in the 1980s by Cambridge scientists, phage display is an immensely powerful research tool that has already led to the discovery of a groundbreaking treatment for auto-immune conditions including rheumatoid arthritis and Crohn’s disease, called adalimumab (Humira).

The technique relies on the innate ability of our immune systems to generate a huge diversity of different antibodies so that we can cope with whatever the world throws at us, and it works like this:

First, researchers take samples of antibody-producing immune cells – called B cells – from a number of healthy volunteers. These samples contain millions and millions of cells, and each one contains individual unique genes encoding the instructions that make up the two main parts of an antibody, known as the heavy and light chains.

Using simple lab techniques, the scientists can copy all of these instructions to make billions of different combinations of heavy and light chains.

Next, all these unique antibody genes are individually packaged up into viruses known as phages, which normally infect and multiply inside bacteria.

Finally, a hundred billion of these loaded phages are pooled together in a single tiny droplet of liquid, referred to as a ‘library’.

Then comes the really clever bit.

Going fishing

These human antibody genes can still work inside a phage, meaning that each one makes a unique antibody ‘hat’ to wear on its surface. And (in theory) there should be antibodies within the phage library that recognise any biological target – whether that’s a molecule floating in the bloodstream that encourages tumours to grow, a piece of the molecular ‘Velcro’ that enables cancer cells to spread, or anything else.

Using their chosen target as bait, our Alliance team can then go fishing for phages. Because the target molecules are coupled to tiny magnetic beads, it’s easy to pull them back out of the test tube using a magnet, along with any phages whose antibody ‘hats’ allow them to recognise and stick to the target.

This initial fishing trip pulls out many different phages, each making a different antibody that recognises the target.

The next challenge is to find the one with that sticks to its target the strongest – meaning that it’s likely to be a potent and effective drug.

To whittle down this pool of potential antibody ‘fish’ to one big catch, the researchers repeat the selection process several times, each time using more stringent procedures to find the best antibodies. The team can also use genetic engineering to further tweak the antibody genes, making the antibody even more potent for therapy. Only then can it be taken forward as a potential treatment for testing in clinical trials in cancer patients – a process that can take several years.

Watch this short animation to find out more about how the whole process works:

Landing a catch

MedImmune currently has more than 100 new antibodies moving through various phases of testing and clinical trials for a wide range of applications, ranging from asthma and arthritis treatments to novel vaccines. All of these discoveries rely on solid knowledge of the biological processes underpinning each disease.

With phage display, as with so many things in life, you get out what you put in. Generating effective, safe antibody treatments is entirely dependent on identifying suitable targets, which is why we’ve teamed up with MedImmune to share our huge wealth of knowledge about the faulty genes and molecules involved in cancer.

We’re also keen for our researchers to come forward with bright ideas for new targets that might lead to life-saving cancer therapies in the future – please visit the lab website if you’re a scientist who’d like to get involved.

The opening of our new joint lab is an exciting time for both Cancer Research UK and MedImmune. The researchers certainly have their work cut out, as we’re hoping to have the first candidate antibody ready for clinical trials by late summer 2019. Let’s get fishing!

Kat