Page 117 - Binder2

Delivering a biologic through the gut doesn’t just avoid a
flare-up of adaptive immunity—it actively teaches the
immune system to accept the molecule. It recruits
CD103⁺ dendritic cells to present the antigen in a
tolerogenic context. It seeds Tregs systemically. It rewrites
the immune “story” surrounding the drug from foreign
threat to benign exposure.

That’s not delivery.
That’s immune instruction.

By contrast, subcutaneous or intravenous delivery bypasses
this tolerance machinery entirely. It drops a highly
engineered, foreign protein directly into immune
surveillance zones—where dendritic cells are primed for
defense, not peace. It's like walking through a bull pen in a
blood red tuxedo.

The result? Heightened vigilance, increased
immunogenicity, and a higher likelihood of anti-drug
antibody development over time.

Designing for immune durability means starting with the
immune system’s architecture in mind.
It means choosing routes and vehicles that align with how
the body learns what to ignore—not just what to attack.
It means treating CD103⁺ dendritic cells not as background
biology, but as collaborators in therapy design.

Because if the goal is to stay in the body long enough to do
real work, a biologic has to earn its place.
And the gut—quietly, elegantly—offers the blueprint.

Next comes the composition of the drug itself.

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