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Post# of 252658
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Re: DFRAI post# 202508

Monday, 07/11/2016 1:40:55 PM

Monday, July 11, 2016 1:40:55 PM

Post# of 252658
CAR-T on/off

1. To ensure that CAR is strong enough and persistent enough to generate anti-cancer response.



Sorry, not following this. How is strength and persistence dependent on the on/off switch? I don't think turning the CAR-T "off" increases persistence in any way.

2. To be able to control Cytokine release storm
3. Control neurotoxicities



Completely understand the importance of those two points. But they point to turning it off. When does turning it back "on" become relevant if, for example, you have CAR-T induced neurotoxicity?

Able to fine tune the CAR and immune response = tolerable treatment, optimized etc



In between variable person-specific manufacturing and difference in persistence lengths, compounded with small molecule availability (to turn on/off), I think it's hard to reasonably expect a company to be able to fine tune the CAR-Ts all that much. I think it's on or off, but little chance of being able to make it 25%, 50% or 75% on. That's a level of control that will be very difficult to achieve.
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