Many diseases mutate as they progress, but HIV is a genius at changing to lie undetected in infected cells and avoid the body’s immune response. But now, scientists from Oxford-based Adaptimmune, in collaboration with the Universities of Cardiff and Pennsylvania, have engineered immune cells to act as ‘bionic assassins’ and see through HIV’s many disguises.
When viruses enter our bodies, they hijack the machinery of host cells to replicate and spread infection. When our body’s cells are infected with a virus, they expose small parts of the virus on their surface, offering a ‘molecular fingerprint’ called an epitope for killer T-cells from the immune system to identify.
This triggers an immune response, eliminating the virus and any cells involved in its production.
As with other viruses, HIV enters the body and replicates itself quickly. However, it also has the ability to mutate rapidly, swiftly disguising its ‘fingerprints’ to allow it to hide from killer T-cells.
Adaptimmune’s technology works at two levels. First, it substantially increases the potency of what are called T-cell receptors in the body to recognise all the mutations which HIV uses to escape detection. Second, it targets the killer T-cells specifically at HIV.
Chief executive James Noble said: “T-cells are our business, but actually following this line of research came as a result of tests on a patient who was HIV positive.
“Despite being HIV positive for 15 years, he had never developed full-blown Aids. We found that his T-cells were able to detect all of the HIV variants, so we started looking at why.”
The results so far are very encouraging. Adaptimmune’s tests in the laboratory have shown that their bionic assassins not only recognise every HIV variant — at least 12 — but also clear all the infected cells, too.
That the assassins recognise all the variants came as a pleasant surprise to the scientists. Normally, one course of treatment will hit one mutation, followed by modified treatments to target others.
But while this is a breakthrough, Mr Noble is not getting too carried away.
He said: “What happens in the laboratory and what happens in the human body are two very different things. Nobody should get any kind of idea we’ve found a complete cure for Aids.”
Every time HIV mutates, the new variant is weaker than its predecessor. The prediction is that the new treatment will not actually kill all HIV cells, but leave a very weak virus that is easier to control.
Adaptimmune’s process is yet another in the field of personalised medicine; in this case very personal, as it uses the patient’s own cells.
T-cells are taken from a patient and a gene added to increase potency and specificity. Some four to six weeks later, the patient receives an infusion of the modified cells. Sufficient cells are harvested initially to allow for repeat treatments.
“It’s an adaptive therapy, hence our name Adaptimmune” said Mr Noble.
Scaling up the therapy to a mass-market level is simply not possible right now. Harvesting and modifying cells from hundreds or thousands of patients would demand huge facilities and there are very few centres which can undertake the work.
The equipment used is not high-tech, but the strict regimen and quality control demanded mean specially-trained staff and dedicated laboratories. The University of Pennsylvania is one of the centres.
Clinical trials are scheduled at the university later this year, and will test two kinds of T-cells to see which is better.
Pennsylvania’s university is well-placed to conduct the trials, having conducted about 25 such tests using similar technology. The US medical system differs from the UK and lends itself to these kind of trials.
While UK care is geographically based, the US has disease centres and these attract patients from all over the country. Such centres can see as many as 1,000 patients a year, a significant number in clinical trial terms.
Adaptimmune’s trials will focus on two key questions. Can the treatment knock down the HIV cells and will the virus return? The answer to the first question will show almost immediately, the answer to the second will take nine months.
Being a treatment that provokes an immune system response, trial regulation is stringent and recruitment of patients slow, in case side effects show.
Mr Noble was formerly chief executive of Avidex, acquired by German company MediGene. Buying back the T-cell technology from MediGene, Adaptimmune was founded in 2008.
He is now also chief executive of sister company Immunocore and they share premises at Milton Park. With venture capital firms reluctant to invest, Mr Noble has found private backers.
“Our collaborators provide so much, particularly time, so our running costs are low and our staff numbers here are small.
“The current Aids drugs cocktail can be effective, but it eventually damages the immune system. Looking to the future, we hope that our treatment really works and can be scaled up to help the millions of HIV and Aids sufferers across the world.”
Comments: Our rules
We want our comments to be a lively and valuable part of our community - a place where readers can debate and engage with the most important local issues. The ability to comment on our stories is a privilege, not a right, however, and that privilege may be withdrawn if it is abused or misused.
Please report any comments that break our rules.
Read the rules hereComments are closed on this article