Resetting Severe Allergies at Their Cellular Source

Thank you, Daniel, for having me.

We're going to talk about allergic and mast cell-mediated disease, allergene, and its use of an in vivo mRNA CAR therapies to selectively eliminate pathogenic mast cells and reset immunity.

Let's start with the problem allergene is trying to solve.

What's wrong with the current approaches to treating severe allergies and mast cell-mediated diseases? What are the limitations of today's standard of care?

Today, individuals that have this severe form of allergies, the life-threatening ones, they have to have a continuous treatment that modulates the symptoms or modulates the ability to not have a reaction.

But this is a lifelong treatment that they have to be on.

And there's no good way to prevent a reaction from happening.

A classic example of the antihistamines that you have to take that control the symptoms, but there's no treatment available that treats the root cause of the allergies that these individuals suffer from.

And what does life look like on a daily basis for someone with severe allergies or mast cell activation or recurrent anaphylaxis?

It's a daily fear that... avoidance and uncertainty you have that you're one bite away from having to go to the ER if you have a food allergy or one exposure away from having a severe reaction.

That fear is not only for the individual, but also for the family members that are with you, whether you're an adult or a child.

So these, I would say fear is the number one daily aspect that these patients suffer from.

Can you explain what a mast cell is and their role in the immune system? And what's the mast cell doing that makes these such stubborn and dangerous diseases?

The mast cell is an immune cell that's distributed throughout your body.

It sits in your lungs, in your gut, in your skin.

And they... get armed to things that shouldn't really cause disease.

They get armed to food, to various, could be anything that someone gets sensitized to.

In any triggers like bee stings or medications, or even just anything that can touch the skin could cause these mast cells to trigger.

So there's these fundamental cells that are there for wound healing and their natural defense for parasitic diseases.

They go awry, and they then get armed to all kinds of triggers that is what causes them to release the factors and cause these severe allergies.

You've had experience in oncology and immunotherapy.

How has that shaped the way you think about allergy and mast cell disease as an immune engineering problem rather than just a matter of symptom control?

Yeah, mast cells are immune cells like other immune cells, such as B cells, where a lot of the current immunotherapies have focused on.

And it causes diseases in a similar pattern.

And the whole concept of an immune reset, which was pioneered in cancer and autoimmune disease with cell therapies, where you can target a B cell, that's the cell type that causes B cell cancers and also autoimmune diseases.