BousWakebo OP t1_jdvglq6 wrote on March 27, 2023 at 2:26 PM

The glycocalyx is developed with high levels of cell-surface mucins, which are thought to help protect the cancer cell from immune cell attack. However, up to now, there has been limited understanding of this barrier particularly as it relates to cell-based cancer immunotherapies.

These types of treatments involve removing immune cells from a patient, modifying them to seek and destroy cancer, and then putting them back into the patient’s body.

“We found that changes in the thickness of the barrier that were as small as 10 nanometers could affect the antitumor activity of our immune cells or the engineered cells used for immunotherapy,” said Sangwoo Park, a graduate student in Matthew Paszek’s Lab at Cornell University in Ithaca, New York.

WoolyLawnsChi t1_jdw392l wrote on March 27, 2023 at 4:55 PM

>the thickness of cancer cells' glycocalyx is one of the major parameters determining immune cell evasion and engineered immune cells work better if the glycocalyx is thinner.
>
>As a result of these findings the researchers then engineered immune cells with special enzymes on their surface to allow them to attach to and interact with the glycocalyx. They then found that these specialized immune cells were able to overcome the glycocalyx armor of cancer cells,

If I am reading this correctly the discovery isn't some new "drug"

instead it will make existing immunotherapies more effective

Phoenix5869 t1_jdw9fnf wrote on March 27, 2023 at 5:35 PM

> it will make existing immunotherapies more effective

That’s good to hear, but it’s a far cry from what the title implies

ConversationOk4414 t1_jdzgzfa wrote on March 28, 2023 at 9:45 AM

They’ve successfully eradicated a form of cancer (I don’t remember which) in their entire study group using this technique.

Solid_Hunter_4188 t1_jdw7gdn wrote on March 27, 2023 at 5:22 PM

Sounds like a selection/gene therapy done specifically to tcell or NK’s to either increase the number of detectors or improve binding of existing MHC

Brain_Tourismo t1_jdyxij3 wrote on March 28, 2023 at 5:15 AM

I thought they had engineered enzymes onto the existing NKs, no? Sure it is an extra step but well worth it.

zeek912 t1_je0gj13 wrote on March 28, 2023 at 3:03 PM

This is pretty old news in the cancer biology field and even older news in the Glycobiology field but I'm happy to see it going more mainstream!

The main mechanism behind mucin/glycocalyx mediated immune evasion is increased levels of sialylation of mucin glycan structures. These densely sialylated proteins interact with a class of immune modulating proteins on immune cells called Siglecs (sialic acid binding immunoglobulin like proteins). These Siglecs bind sialylated structures and tell immune cells to ignore otherwise antigenic cells.

Researchers are trying a couple of different ways to address this, one of my favorites involves a chimeric antibody with a sialidase domain attached. I believe that one was the Bertozzi lab (a recent Nobel prize winner) and that one is already well into clinical trials.