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immune system, silence it, sedate it—whatever it takes to
get the molecule in and keep it there.

This approach was understandable when our tools were
limited. But today, we know more. We know the immune
system isn’t just reactive—it’s relational. It remembers. It
learns. And it can be taught to trust—if we design with that
intention.

We don’t need to defeat the immune system. We need to
coexist with it.

This requires a cultural reset:

• From targeting to teaching:
It’s not enough to bind to a receptor. Therapies must
educate the immune system—using pathways like
oral tolerance, liver-based antigen presentation, and
mucosal signaling to say, “this is safe.”
• From suppression to harmony:
Co-immunosuppressants shouldn’t be standard
accessories. They’re crutches for poorly designed
therapies. The goal must be endogenous
acceptance, not brute-force immune silence.
• From escalation to expectation:
The fact that we normalize dose increases and
therapeutic switches is a symptom of failure. The
default mindset should be:
o If it escalates, it failed.
o If it’s rejected, it wasn’t designed right.
Expectation should shift toward minimal
intervention, sustained response, and
immune compatibility from Day One.
• From silence to transparency:
Right now, ADA rates are hidden in footnotes.
SLOR is framed as “disease progression.”

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