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DFRAI

07/08/16 10:09 AM

#202451 RE: DewDiligence #202450

Juno - ZIOP benefit perhaps

ZIOP has better tech than Juno and Kite
Their tech can avoid CRS and other toxicities in my view.
Recently they modified their agreement with XON allowing ziop to keep 80% of profits = takeover target in the next 6 months. GLTA
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dewophile

07/08/16 10:28 AM

#202454 RE: DewDiligence #202450

surprising since (supposedly) younger pts can tolerate the SEs from CAR-T better
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Biowatch

07/10/16 3:05 PM

#202503 RE: DewDiligence #202450

3 deaths in Fludarabine arm from cerebral edema, none in other arm.

Fludarabine is used to clear out existing cells to make room for expansion of the CAR-T cells. It is used routinely in bone marrow transplantation.

Fludarabine itself can cause toxic side effects, especially at high doses, but presumably the combination therapy is the problem.

Fludarabine may have allowed too much room for the CAR-T cells to expand, allowing a cytokine storm to occur.

Edema results when capillaries become leaky and too much fluid builds up, resulting in potentially fatal edema. It also permits greater access for circulating T cells to infiltrate the body.

Greeter infiltration could cause inflammation and cytokine release that increased the leakiness and allowed greater T cell infiltration and more leakiness and CAR-T expansion in a cycle that led to fatal cerebral edema.

This could be a good argument for the ability to slow down the activity of CAR-T cells.
See post #msg-123763045

See also:
http://blogs.sciencemag.org/pipeline/archives/2016/07/08/car-t-deaths-cannot-be-good#comment-271174