Hyperprogression % in PD-1 inhibition studies is bad, then there is myocarditis – adding CRISPR in that equation is lethal.

20/21 patients died in this PD-1/CRISPR trial for esophageal cancer.

Hyperprogression is one possible reason – maybe myocarditis for this case?

Also,  a 2019 shows PD-1 KO  impairs the anti-tumor potential of CAR-T cells because it inhibited T cells’ proliferation activity.

Using CRISPR to make edits (and 3, like in the UPenn trial) exposes the patients to more dangers arising from off-targets, translocations, etc etc.

There is literally no study showing the effect of T-cells after CRISPR edits (pls let me know if you do) – and I have looked at a lot (20+ studies).

Read this twitter thread for anecdotal cases of hyperprogression.

 

“Hyperprogression during immunotherapy: do we really want to know?” (2017, July)

Asks Champiat, who first reported hyperprogression (HPD) in 2017,  There are several other studies reporting this nowadays.

While in 2017, 12/131 (9%) patients showed HPD, a much larger study by Kim (July 2019) et al. showed  “19% (45/237) of NSCLC patients treated by anti-PD(L)1 blockade presented with HPD”. This is a large number (%).

Still not 100% as in PD-1 trial.