Off-the-peg anti-cancer cell treatment

New cancer treatment that could forego the need for specialised individual treatment
27 October 2022

Interview with 

Waseem Qasim, UCL Great Ormond Street Institute of Child Health


Cancer cells


In recent years, doctors have begun to treat cancers of the blood, called leukaemias, by reprogramming some of a patient's own white blood cells to target their own cancer. This is called CAR-T cell therapy. It's very effective, but the problem is that it's also very expensive, because it has to be done on an individual patient basis. It also takes a lot of time, delaying treatment. Much more effective would be to engineer cells that anyone could use. And this week researchers at UCL's Institute of Child Health in Gt Ormond Street, London, have announced that they've done just that. They've engineered white blood cells that have been disarmed and cloaked so they don't attack healthy tissue, or get taken down by a person's own immune system, and instead they go after exclusively leukaemia cells. And because they are ready to go immediately, there are no treatment delays. Waseem Qasim has now treated 6 children this way....

Waseem - There are certain types of blood cancer leukaemias that are now treatable by using the power of the immune system that can be reprogrammed. So they go around the body and clear up leukaemia that's otherwise resistant to chemotherapy or has come back after chemotherapy.

Chris - How do you actually reprogram an immune cell?

Waseem - Well, we take the white blood cells, they're taken to a laboratory and while they're there we use a disabled virus to add a chunk of DNA which programs for a new, think of it as an arming device, that can then recognize and target the cells towards abnormal cancer cells. Usually they're then frozen and undergo a round of quite stringent tests before they're returned to the hospital where the patient receives them as an infusion. And then it's the question of waiting for a period of days or weeks to see if the cells are going to manage to clean up the leukaemia.

Chris - What have you done to improve on this then?

Waseem - At the moment, these are patient-bespoke therapies and what we've tried to do is make them available off the peg, if you like, or off the shelf. So to do that we have to add in some extra engineering steps, which means that they can be infused into multiple recipients without the need for very close matching.

Chris - You're saying you're going to make available to anybody, cells that have been manipulated in this way to go after cancer. So it doesn't matter who they are, they can have these white blood cells and anyone can use them. So how do you stop them being recognized as foreign when they go into the cancer victim's body and how do you also stop them attacking things they shouldn't?

Waseem - Yes, that's two very important questions. So if I deal with the second one first, we can disarm the cells by removing their own T-cell receptor, which is their normal arming device. It's the normal weapons they carry on their surface to attack viruses and so on. So we take those away and then we reprogram the cells so they only recognize a single target, and at the same time we remove one of the flags of the surface of the cells that will make them invisible to one of the chemotherapy antibodies we use to subdue a patient's immune system before the cells are actually given. So all of that together means the cells will have a free run for two to three weeks after infusion in a patient without really being challenged by the patient's own immune system. And we think that's actually long enough to get a deep clearance of leukaemia.

Chris - And does it work?

Waseem - Well, we treated six children out of which four successfully reached a stage of remission, by which we mean within 28 days we couldn't detect leukaemia anymore. Now, over a longer period of time, two of those patients are still clear of leukaemia. The furthest one out is well over a year out now. Now, unfortunately, in a couple of the others, the disease did eventually come back. So we're looking at why that happens and how it manages to evade or escape the effects of cells over a longer period of time.

Chris - How would that outcome compare with what we consider a gold standard practice - not doing your new approach?

Waseem - Generally speaking, we think the longer term outcomes won't be far off those achieved by patients receiving their own cells. Bearing in mind at the moment where only treating the patients that have not been able to have the treatment from their own cells for various reasons. And so they tend to be the more advanced patients that are coming for these type of trials. I think it'll take a longer period of time to work out what the comparisons will be. Then ultimately you'd have to run a comparison study with two groups of very similar patients to find out what the actual overall rates are.


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