Replies to post #202456 on Biotech Values

[poorgradstudent]

CAR-T etc...

I am curious if this news will ultimately benefit those players with suicide switches

I've been thinking about this for a while now as reports of CNS AEs with CAR-Ts are not new. I don't buy the company line that flu or flu/cy is the cause; this preconditioning regimen simply allows the engineered T cells to be more effective. And at this point, their efficacy is, to an extent, part and parcel with their AEs.

In that regard, I don't think suicide switches are going to be the key for CAR-Ts in the long term. The suicide switch effectively removes the engineered cells from the circulation, so it also kills efficacy. The point of an adaptive strategy is to minimize AEs while maintaining efficacy and/or maximize efficacy while maintaining AEs. Suicide switches reduce AEs by removing efficacy, and I don't see that as a meaningful long-term strategy for CAR-T.

I think optimizing the CAR-T construct's constituents along with prophylactic measures such as tocilizumab (IL-6 blockade) to minimize cytokine activity are more plausible modifications going forward.

[lgonber]

Not sure about the switches but for sure the news benefits bi- specifics. The companies you mentioned and AMGN as well