This is how T cells work “with turbo”

The immune system in our body is a fascinating biological machine that protects against any type of threatsuch as hateful tumor cells. But these cells are really intelligent, and have the ability to camouflage themselves from our defenses, as happens in prostate cancerwhere tumor cells look so much like healthy cells that our defenses barely recognize them or do so with such weak force that the tumor manages to escape.

What were we doing until now? The medical solution was to increase the ‘affinity’ of the defensive cells to the maximum so that they destroyed the tumor cells. The problem? That sometimes they over-braked and attacked healthy tissue, making it more harmful than beneficial. But now this is something that we are trying to solve with the design of “hooks” on a molecular scale.

The problem. If we delve deeper into this problem, we must know that T cells, which are part of the immune system, have receptors on their surface that literally bind specifically to the foreign proteins of tumor cells in order to identify them, as if it were a nightclub bouncer asking for ID to detect those who cannot enter.

In prostate cancer, one of the targets to look for is the PAP protein, which tells the immune system that it should start attacking, although the problem is that the affinity is not very good, so they literally missed identifying many of these. The problem is that increasing the affinity of this cell causes the opposite effect, by becoming hyperactive and developing a ‘cross-reactivity’ that mistakenly attacks the healthy organism and generates a high level of toxicity.

In this way, it was necessary to increase the affinity, but without it being toxic.

The solution. This is where the brilliance comes in. a new job published in Science that is based on proven concepts by previous teams who tried to achieve this better affinity. What they saw here is that the solution was not to increase the “glue” of the cell in general so that it would stick together better, but to design what they have called ‘catch bonds’.

Catch bonds. To understand how it works, you simply have to imagine a seat belt or a fishing hook. Under normal conditions, the bond is quite soft, but if a large mechanical force is applied, the bond changes its structure and grips much more tightly.

In this way, the scientists took a weak natural receptor specific for the PAP protein and introduced very precise mutations into it. The result is a genetically modified receptor that acts like a hook.

Better cells. By entering these coatch bonds, The researchers managed to create T cells ‘with turbo’ and in the tests they showed that these cells could bind much better to prostate cancer cells and also managed to destroy them in a more efficient way.

But the most important thing here is that a very low cross-reactivity is maintained, so they have the ability to ignore healthy tissues and only deploy the destructive potential when the mechanical “hook” comes into action on the specific target.

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