By Fernanda Ferreira
A cancer drug could one day be taken to prevent life-threatening allergic reactions, including anaphylaxis.
Mice pre-treated with the drug did not suffer an anaphylactic reaction when injected with an allergy trigger. Mice, who had received two doses of the cancer drug a few hours before the trigger, also recovered faster and were less likely to die when injected with a lethal dose of the trigger than mice that didn’t get the drug, researchers report in an upcoming issue of the Journal of Clinical Investigation.
As much as five percent of the US population has suffered anaphylaxis, a condition characterized by rashes, nausea, vomiting, difficulty breathing and shock. While rare, it can be fatal. There are currently no drugs that prevent anaphylaxis. Patients with food, drug or insect allergies rely on carefully avoiding triggers and carrying a counteracting medication called epinephrine with them at all times. Caution is not always enough. An estimated 63 to 99 people die of anaphylactic shock each year in the US.
For individuals with severe allergies, a preventative pill could be a game changer. A study conducted in 2019 by the Allergy and Asthma Foundation of America found that the burden of food allergies isn’t just physical. “[It] has significant impacts on mental and emotional health,” Hannah Jaffe, a research analyst at the foundation, wrote in an email. Social activities, like birthday parties and eating out, as well as air travel and vacations are filled with uncertainty and the fear of a reaction. “So much so that many choose to miss out on social events,” Jaffe says. A preventative pill “would be a huge relief to many individuals and families living with food allergies.”
About a decade ago, Bruce Bochner, an allergist now at Northwestern University and one of the study’s authors, was approached by Pharmacyclics, a company that developed the first of a new type of drug called BTK inhibitors, for treating certain blood cancers. These drugs bind to and inhibit the activity of Bruton’s tyrosine kinase (BTK), an enzyme that is necessary for normal development in certain types of cells. Two such cells are mast cells and basophils, which play an important role in allergic reactions. Pharmacyclics’ researchers had noticed that basophils in cancer patients taking the inhibitor didn’t react as strongly to allergic triggers.
Basophils and mast cells are filled with pouches carrying histamine and other molecules. When prompted by an allergen, such as an insect bite or peanuts, they dump these into the body causing an allergic reaction, including anaphylaxis. BTK inhibitors work by barring the release of these reaction-triggering molecules, opening the possibility of using these cancer pills to prevent severe allergic reactions.
In the new study, human mast cells treated with the BTK inhibitors in culture dishes didn’t release the contents of their pouches. Additionally, human lung tissue, which constricts during anaphylaxis, didn’t contract when presented with a trigger after treatment with the inhibitor, Melanie Dispenza, an allergist and immunologist at Johns Hopkins, and her colleagues discovered.
To investigate whether BTK inhibitors might prevent anaphylaxis in people, Dispenza and colleagues engineered mice to carry human mast cells. Those mice were more likely to bounce back from a potentially lethal allergy attack if they got BTK inhibitors.
If the findings hold up in human studies, people with food and other life-threatening allergies might not have to worry so much about accidentally eating their allergy trigger or getting stung by a bee.
But, Syed Shahzad Mustafa, an allergy specialist and chair of the medical advisory board of the Food Allergy & Anaphylaxis Connection Team, urges caution. “You don’t want someone taking [a preventative pill] and that resulting in more cavalier behavior in a food allergy world,” he warns. Using the pill as needed before trips or high-risk situations would be okay, Shahzad Mustafa believes, but “you don’t want to be changing the mind set of strict avoidance.”
Beyond preventing allergic reactions to food, Dispenza envisions other scenarios where a BTK inhibitors may play an important role. Such uses might include protecting people while their immune systems are trained to tolerate allergy triggers or while taking an antibiotic to which the person is allergic but there’s still work that needs to be done, including determining how safe these inhibitors are for people without cancer and for children. “Human studies are absolutely necessary to make sure that this will be a real possibility of something that can prevent anaphylaxis or not,” Dispenza says. Those drugs are already approved by the U.S. Food and Drug Administration for treating cancer patients and, Dispenza says, human studies will begin at Johns Hopkins soon.
Fernanda Ferreira is a science writer and masters student at MIT’s Science Writing program who has written for Science in the News, MIT News and MIT Technology Review. She holds a Ph.D. in virology from Harvard University. Follow her on Twitter @FerniFerreira.
This story was produced as part of NASW's David Perlman Summer Mentoring Program, which was launched in 2020 by our Education Committee. Ferreira was mentored by Tina Hesman Saey.
