Erik Wambre. Photo: Benaroya Research Institute The study, published in Science Translational Medicine in August, shows there is a key group of cells – dubbed Th2A cells – only present in people with allergies. We spoke to lead researcher Erik Wambre, PhD, to find out more about his promising findings.
Allergic Living: Is it that clear-cut – if you have these particular cells, you have some sort of allergy?
EW: Yes. Allergy is well-known to be a Type 2 immune disease. A type of cells called Th2 drive the allergic response. But those cells are also very good for you. They protect you against viruses and parasites.
We found a way to distinguish between the good cells involved in fighting the parasites, bacteria and infection, and the ones involved in allergy. However, these cells don’t tell you what you are allergic to.
AL: How were you able to identify this subset of Th2 cells?
EW: In our institute, we have molecules that can really stick to cells of interest. If we want to look at the cells involving the flu, we can go through the cells specific to flu. We can do the same thing with allergy.
We looked at the cells involved in allergy in allergic patients and compared those cells with the good Th2 cells. We looked at 200 different properties in those cells, and in the end we found five unique characteristics in the cells involving allergy.
AL: Why is this significant?
EW: Those cells are the starting point of allergic disease. Our hope is that, in the future, by drawing a very small amount of blood, we could find out if kids are at high risk to develop food allergy, for example. Right now, most parents realize their kid is allergic when they go to the emergency room after the accident happens. We would like to have a way to predict food allergy earlier.
AL: How far away is something like that?
EW: We still need to perform a lot of studies. We are collaborating with a biopharmaceutical company with ongoing clinical trials for peanut oral immunotherapy. [Editor’s Note: The company referred to is Aimmune Therapeutics, which at the time of writing was in Phase 3 trials for AR101, a peanut oral immunotherapy product. The FDA has now approved the product.].
The idea is to document what the impact of immunotherapy is on those cells, and see if we can stratify the patient based on the type of cells they have. We have to document a lot of patients and then we will be able to talk to the FDA showing them there is a strong correlation between the development of food allergy and the presence of those cells.
AL: The study you published is the culmination of seven years of research. Why did it take that long?
EW: The molecule we used to track those allergy-specific details is very expensive, and you also need a lot of blood because the frequency of those cells is very low. There are only 1 to 5 per every million cells. For every cc (cubic centimeter) of blood, you have one million cells. So we needed a minimum of 200 to 300 cc of blood per test.
We started with tree pollen, then grass pollen, and we observed the five differences were present for both allergens. Then we moved to food allergy, looking at peanuts, and then to mold, cats and dust mites.
We found that whatever the type of allergy, it was always the same type of cell involved. For the first time we may have an opportunity to find drugs that will specifically stop or destroy these pathogenic Th2 cells, which might cure allergy in general.
AL: What needs to happen for a such a treatment to be found?
EW: With OIT, we observed the decrease of this subset of cells highly correlated with clinical benefit. So if you stop these cells, it appears the patients will be better.
If we take a blood draw from an allergic patient, we can screen a lot of drugs and see how we can destroy the Th2A cells. This is something Big Pharma is doing every day. For them, it’s most important to have the target. In cancer, the target is the tumor, and they try to kill the tumor without harming the good cells.
We want to see how we can destroy the Th2A cells, without touching the good Th2 cells.
David Jeong and Erik Wambre. Photo: Benaroya Research Institute AL: What’s next in your research?
EW: We are really focused on a way to make a link between the risk of having an anaphylactic reaction, or just having gastrointestinal symptoms.
Food allergy is more complicated than other allergy, and the Th2A story is only part of the story. With food allergy patients, there’s also another type of cell that’s involved.
We want to see whether the presence of Th2A cells in food-allergic patients makes them at higher risk of having anaphylaxis, compared to a patient that has a little bit of Th2A but more of this other subset. We think the other subset will be more related to the gastrointestinal symptoms, like vomiting and diarrhea. I have two data scientists on my team who work on trying to correlate the type of immune response with symptoms.
As mentioned, we are also currently following 50 patients in a Phase 3 peanut oral immunotherapy clinical trial. Some patients will have side effects during treatment, and some patients see a clinical benefit, while others don’t.
We would like to see if we can predict that before the treatment. The study will be finished in November, and my hope will be to present those data at the American Academy of Allergy, Asthma & Immunology meeting next March.
AL: How did you get interested in allergy research?
EW: I did my PhD in France and worked with a pharmaceutical company that was a leader in allergen immunotherapy.
Because of this background, I first focused this research on pollen and dust mite allergy. When I started to look at food allergy, I realized that it is almost the same kind of response we see in pollen. I was really surprised, because I thought, ‘Why don’t we have any treatments if we have the same type of cells involved?’
What I like about food allergy is I feel like I can really help the patient. Food allergy is a growing issue, and it’s not only an issue for the kids, but for their parents. I really think that research in food allergy will dramatically improve the way of life for families.
Main funding for this research was provided by: National Institutes of Health (NIH), Food Allergy Research & Education (FARE) and the Immune Tolerance Network (ITN).
