Mind the gap: GSK and UK scientists say smaller is better for some biopharmaceuticals

By Gareth Macdonald contact

- Last updated on GMT

A bacterium (MRSA, yellow) being ingested by an immune cell
A bacterium (MRSA, yellow) being ingested by an immune cell

Related tags: Immune system

UK researchers working with GSK say a newly identified immune cell communication mechanism could explain why some drugs don’t work and drive development of smaller, large molecule meds.

It is a well-established principle that when an immune system cell encounters a foreign body or tumour it communicates this interaction by secreting chemical signals that prompt responses in other cells of the immune system.

Now thanks to research​ by scientists at Manchester Collaborative Centre for Inflammation Research we know these chemical signals must cross gaps between the cells and that only small molecules are capable of making the journey.    

Project leader Dan Davis said: “We studied the immune system and then stumbled across something that may explain why some drugs don’t work as well as hoped. We found that immune cells secrete molecules to other cells across a very small gap.

Professor Davis added that: “This happens when immune cells talk to each other and also, when they kill diseased cells. But crucially, some types of drugs aren’t able to penetrate the gap between the cells. So they can’t easily reach targets within the gap, to work effectively​.”

Delivering results

The team – which used drugs developed by UK-based pharmaceutical firm GlaxoSmithKline (GSK) to assess intracellular communication – also found that even when one immune cell attaches to another the gaps are maintained.

The researchers say their findings mean drugs that target immune cells need to be small and suggest that larger therapeutics are simply too large to cross the intercellular gaps.

Davis said: “Antibody proteins, for example, are too big and aren’t able to get into the gap between the cells - they’re even cleared away when cells meet. To make them more effective they must be smaller - something that GSK is working on​.”

In addition to prompting the development of smaller drugs, GSK and the Manchester team are also examining ways of turning off damaging immune responses in auto-immune diseases.

Simon Chell, from GSK’s Biopharm R&D team, explained that: “A lot of important targets for future medicines are in the very small gap between cells. This research demonstrates why in certain cases we may need drug molecules to be smaller to work effectively.”

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