CAR-T, why it's not ready for MPNs

[EPguy]

Today's CNN has an article about CAR-T being curative for leukemia CLL. So I checked it out a bit further.

mpnresearchfoundation.org/n...

As I understand it CAR-T looks at the antigens on the surface of the cells, and cannot see inside the cells. This is loosely like the Covid vaxes looking at the spike proteins but not inside the virus cell. There have been some covid vaxs that tried to look inside (since it does not mutate much there) but it's not promising so far.

So CAR-T kills every cell with this exterior antigen signal, good and bad. In the link:

<< It turns out that human beings can live without their B (good and bad leukemia affected) cells for a very long time indeed>> But

<<If CAR T cells were to target myeloid antigens indiscriminately, both abnormal and normal myeloid cells would be killed. We cannot live without myeloid cells for long, since they produce the red blood cells that we need to carry oxygen, platelets for blood clotting, and the white blood cells that we need to fight off infection.>>

I think this means for example in Jak2 it would kill all of them and we'd have no new blood makings for a while. But it may have use for CALR,<<Is the CALR mutation a “unique” target because of its location on the cell surface as compared to MPL and JAK2 mutations which are inside cells? ...There is great potential for the CALR mutation to be used as a target for CAR T cells>>

[EmeraldA]

theguardian.com/society/202.... You beat me to it. The article attached is very interesting too.

[EPguy in reply to EmeraldA]

Thanks for the additional info. In that link UNL (London) is working on a 2nd Gen Car-T. It does not seem to be more relevant to MPNs except as above, this should still be a good path for CALR - ET research.

[Wyebird]

Oh fab thanks

[jmctrek]

Thank you for this article. It’s a fascinating read and helps me understand why Car-T is currently not suitable for treating those of us with the jak2 mutation.