4 ms·

Fascinating, this drug (molecule) somehow “unmasks” the cancer cells, allowing the body’s natural immune system to target and destroy them. How does a molecule

Fascinating, this drug (molecule) somehow “unmasks” the cancer cells, allowing the body’s natural immune system to target and destroy them. How does a molecule do that!? Enters the blood stream, is absorbed by the cancer cell, and then…? Blocks some enzyme?

vervez 4y ago
Couldn't read the article but yea, if it's a small molecule, most likely it's inhibiting some protein specific to cancerous cells. In this case, it sounds like it's blocking some protein that blocks human cells' innate ability to produce antigens, which signal to T-cells that they are defective and need to be destroyed. Sometimes we understand the biology after we discover a treatment.
- epgui 4y ago
  It’s not a small molecule, it’s a biologic (antibody). It was designed specifically to do what it does, and not discovered by chance.
instagraham 4y ago
That is the function of checkpoint inhibitors, according to an explanation I got from a cancer researcher after asking a similar question. Essential, cancer cells convince the immune system not to attack them, so these inhibitors target the mechanisms by which they do so to get the immune system to take note of these cells. Hope someone more knowledgeable will correct me if I'm wrong.
- adamredwoods 4y ago
  Cancer cells express proteins that communicate with lymphocytes (white blood cells) to block apoptosis (cell death). We can't target the cancer cells, so we tweak the lymphocytes to block PD-1 receptors, thus ignoring ALL cells that express a lot of PD-L! protein. This unfortunately includes healthy cells.
ohazi 4y ago
It's an antibody. https://en.m.wikipedia.org/wiki/Dostarlimab https://en.m.wikipedia.org/wiki/Dostarlimab https://en.wikipedia.org/wiki/Pembrolizumab https://en.wikipedia.org/wiki/Pembrolizumab
_Microft 4y ago
The name of the drug ends in "-mab" [0] indicating that the drug is based on monoclonal antibodies [1,2]. Those antibodies are tweaked to bind to cancer cells which makes the immune system attack the cancer cells. [0] https://en.wikipedia.org/wiki/Drug_nomenclature#List_of_stems_and_affixes https://en.wikipedia.org/wiki/Drug_nomenclature#List_of_stem... [1] https://en.wikipedia.org/wiki/Monoclonal_antibody https://en.wikipedia.org/wiki/Monoclonal_antibody [2] https://en.wikipedia.org/wiki/Monoclonal_antibody_therapy https://en.wikipedia.org/wiki/Monoclonal_antibody_therapy
- ufo 4y ago
  IIRC, in this particular case the antibodies bind to immune cells. Immune Checkpoints are a mechanism that keeps the immune system from attacking the own body but in cancer it can also stop the immune system from destroying the cancer. The checkpoint inhibitor antibodies remove these restrictions and allow the immune cells to attack the cancer. (The price is that they also become free to attack other things they shouldn't; autoimmune inflamations are common side effects.) https://en.wikipedia.org/wiki/Checkpoint_inhibitor https://en.wikipedia.org/wiki/Checkpoint_inhibitor
  - dekhn 4y ago
    Who the hell designed this computer?
cowmoo728 4y ago
Several varieties of T cells are very dangerous and like to murder other cells. In order to prevent them from going on a rampage, they have a switch called PD-1 that calms them down. This prevents various auto-immune diseases in healthy people. Some varieties of cancer cells release a PD-1 ligand that turns off T cells when they get close to the cancer. So the cancer can "hide" from the immune system. This monoclonal antibody blocks PD-1 on T cells, turning them into unstoppable murderers. The hope is that they preferentially murder the cancer cells. Wikipedia says that ~5% of patients get dangerous side effects from blocking T cell PD-1, probably because the unstoppable T cells attack healthy kidney or liver tissue. But for people with specific types of cancer, the hope is that turning the T cells loose will kill the cancer first.
sam537 4y ago
There are two types PD1 and PDL1 inhibitors. Cancer cells (and our own cells) express PDL1. Our immune cells touch PDL1 with their PD1 and if this connection works then the immune cell does not kill. If the connection does not work (PDL1 or PD1 absent) the immune cell will kill the target cell. These antibodies either block PDL1 or PD1.

vervez 4y ago

Couldn't read the article but yea, if it's a small molecule, most likely it's inhibiting some protein specific to cancerous cells. In this case, it sounds like it's blocking some protein that blocks human cells' innate ability to produce antigens, which signal to T-cells that they are defective and need to be destroyed. Sometimes we understand the biology after we discover a treatment.

epgui 4y ago
It’s not a small molecule, it’s a biologic (antibody). It was designed specifically to do what it does, and not discovered by chance.

instagraham 4y ago

That is the function of checkpoint inhibitors, according to an explanation I got from a cancer researcher after asking a similar question. Essential, cancer cells convince the immune system not to attack them, so these inhibitors target the mechanisms by which they do so to get the immune system to take note of these cells. Hope someone more knowledgeable will correct me if I'm wrong.

adamredwoods 4y ago
Cancer cells express proteins that communicate with lymphocytes (white blood cells) to block apoptosis (cell death). We can't target the cancer cells, so we tweak the lymphocytes to block PD-1 receptors, thus ignoring ALL cells that express a lot of PD-L! protein. This unfortunately includes healthy cells.

ohazi 4y ago

It's an antibody. https://en.m.wikipedia.org/wiki/Dostarlimab https://en.m.wikipedia.org/wiki/Dostarlimab https://en.wikipedia.org/wiki/Pembrolizumab https://en.wikipedia.org/wiki/Pembrolizumab

_Microft 4y ago

The name of the drug ends in "-mab" [0] indicating that the drug is based on monoclonal antibodies [1,2]. Those antibodies are tweaked to bind to cancer cells which makes the immune system attack the cancer cells. [0] https://en.wikipedia.org/wiki/Drug_nomenclature#List_of_stems_and_affixes https://en.wikipedia.org/wiki/Drug_nomenclature#List_of_stem... [1] https://en.wikipedia.org/wiki/Monoclonal_antibody https://en.wikipedia.org/wiki/Monoclonal_antibody [2] https://en.wikipedia.org/wiki/Monoclonal_antibody_therapy https://en.wikipedia.org/wiki/Monoclonal_antibody_therapy

ufo 4y ago
IIRC, in this particular case the antibodies bind to immune cells. Immune Checkpoints are a mechanism that keeps the immune system from attacking the own body but in cancer it can also stop the immune system from destroying the cancer. The checkpoint inhibitor antibodies remove these restrictions and allow the immune cells to attack the cancer. (The price is that they also become free to attack other things they shouldn't; autoimmune inflamations are common side effects.) https://en.wikipedia.org/wiki/Checkpoint_inhibitor https://en.wikipedia.org/wiki/Checkpoint_inhibitor
- dekhn 4y ago
  Who the hell designed this computer?

cowmoo728 4y ago

Several varieties of T cells are very dangerous and like to murder other cells. In order to prevent them from going on a rampage, they have a switch called PD-1 that calms them down. This prevents various auto-immune diseases in healthy people. Some varieties of cancer cells release a PD-1 ligand that turns off T cells when they get close to the cancer. So the cancer can "hide" from the immune system. This monoclonal antibody blocks PD-1 on T cells, turning them into unstoppable murderers. The hope is that they preferentially murder the cancer cells. Wikipedia says that ~5% of patients get dangerous side effects from blocking T cell PD-1, probably because the unstoppable T cells attack healthy kidney or liver tissue. But for people with specific types of cancer, the hope is that turning the T cells loose will kill the cancer first.

sam537 4y ago

There are two types PD1 and PDL1 inhibitors. Cancer cells (and our own cells) express PDL1. Our immune cells touch PDL1 with their PD1 and if this connection works then the immune cell does not kill. If the connection does not work (PDL1 or PD1 absent) the immune cell will kill the target cell. These antibodies either block PDL1 or PD1.