To ohm or to anyone who might know, In the case
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Posted On: 10/12/2025 6:37:36 AM
To ohm or to anyone who might know,
In the case of GBM or any Brain Tumor, we need to get LL into the brain. That means it needs to cross the BBB. I understand that with brain tumors of any sort, there is tremendous inflammation and therefore, the BBB becomes disrupted and many otherwise blocked proteins can now enter the brain. So I know, that is one way.
Also, activated Killer T Cells that have LL attached to their CCR5 can take LL into the brain, but that LL is already used. It is attached to the CD8 Killer T Cells CCR5.
My question is without relying on a disrupted BBB, how does LL enter the brain, freely, unattached, without being carried in via connection with CCR5 of an immune cell?
Also, in this write up, Bank Shot , I make an assumption that in the coming GBM trial, it would be best to use a PD-1 blockade over a PD-L1 blockade.
I say this because, a PD-1 blockade can attach PD-1 receptors on activated CD8 Killer T Cells and subsequently have the ICI block in place even before entering the Brain. However, with PD-L1 blockers, they have no access to the Brain Tumor until they enter the brain. But they can't enter the brain unless the BBB is disrupted. I know there will be some disruption, especially around the site of the tumor, but it can't be depended upon.
What are your thoughts on this?
Lastly, why do you think intra-thecal administration of ICIs was never trialed. It has been proven safe, but do you think the idea of doing a spinal tap weekly was just too much to ask a patient in order to treat an oncology patient with brain mets? Both LL and Keytruda can be given intra-thecal, but do you think this trial would consider it if there was an issue with crossing the BBB for either drug?
In the case of GBM or any Brain Tumor, we need to get LL into the brain. That means it needs to cross the BBB. I understand that with brain tumors of any sort, there is tremendous inflammation and therefore, the BBB becomes disrupted and many otherwise blocked proteins can now enter the brain. So I know, that is one way.
Also, activated Killer T Cells that have LL attached to their CCR5 can take LL into the brain, but that LL is already used. It is attached to the CD8 Killer T Cells CCR5.
My question is without relying on a disrupted BBB, how does LL enter the brain, freely, unattached, without being carried in via connection with CCR5 of an immune cell?
Also, in this write up, Bank Shot , I make an assumption that in the coming GBM trial, it would be best to use a PD-1 blockade over a PD-L1 blockade.
I say this because, a PD-1 blockade can attach PD-1 receptors on activated CD8 Killer T Cells and subsequently have the ICI block in place even before entering the Brain. However, with PD-L1 blockers, they have no access to the Brain Tumor until they enter the brain. But they can't enter the brain unless the BBB is disrupted. I know there will be some disruption, especially around the site of the tumor, but it can't be depended upon.
What are your thoughts on this?
Lastly, why do you think intra-thecal administration of ICIs was never trialed. It has been proven safe, but do you think the idea of doing a spinal tap weekly was just too much to ask a patient in order to treat an oncology patient with brain mets? Both LL and Keytruda can be given intra-thecal, but do you think this trial would consider it if there was an issue with crossing the BBB for either drug?
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