Replies to post #147366 on Biotech Values

[porkchop11]

Mimicking apoptosis (normal cell death) to avoid detection...that is until bavi alerts the killer immune cells. Could that be delayed? I would think.

And remember, bavi can be armed too : )

all imo.

porkchop11

[poorgradstudent]

this immune response may be requiring a bit of time...that's where the 'slower' comment comes from.

For the immune system, passive memory is evident within days. Active memory is evident within weeks, with IgGs developing within 2 months.

That's not slow given the median survival numbers that are talked about. The "slow" explanation is often invoked for cancer immunotherapies, largely by companies that have immunotherapies that don't elicit effective immune responses.

the PS has flipped to the outside on them so they're essentially disguised as normal, dying cells, and bypassed by the immune system

I'm not really sure how this provides a means for the cell to "escape" apoptosis. PS is flipped to the outer leaflet during apoptosis, at which point it is recognized by phagocytes directly (see ref). So if a cancer cell is exposing PS on the outer leaflet, it is doing the exact opposite of disguising itself... it is in fact putting out a very specific signal for phagocytes to come and engulf it. So the disguise angle makes little sense. If anything, the antibody binding the phosphatidylserine would help disguise the cell from the phagocytes.

I would also expect that if this anti-PS antibody was really working, you'd expect bleeding as a mechanistic side effect in patients. Activated platelets expose phosphatidylserine to accelerate clotting (see ref). If anything, the antibody would inhibit this acceleration and decrease the efficiency of clotting.

[vinmantoo]

<PS is not recognized by the immune system as a threat since it's on the outside of regular dying cells, rather than being on the inside as it is in healthy cells.. that's apparently why the immune system doesn't attack cancer cells aggressively; the PS has flipped to the outside on them so they're essentially disguised as normal, dying cells, and bypassed by the immune system... bavi changes that...the immune system then detects nasty cells, and attacks the same cells bavi has latched onto since it targets the PS. this immune response may be requiring a bit of time...that's where the 'slower' comment comes from. >

honestabe,

First of all, apoptosis isn't a term that is applied to cell death. It is programmed cell death. Necrosis is the term used to describe "normal" cell death.

Second, you are describing the ability of the immune system to distinguish between self and non-self. As poorgradstudent (and I) accurately described, there would be no delay once Bavi binds to the everted PS.

I am a bit rusty in my immunology, but I recall the ability of cancer cells to evade the T-cell immune system is linked in a large part to their ability to reduce or eliminate MHC expression/antigen presentation. Natural killer cells attacks cell without MHC on their surface, so cancer cell evasion isn't complete.