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Comment by rqs | Hacker News Reader

So if my understanding was correct, by applying the treatment (Immune Checkpoint Therapy I guess), immune system will clean cancer cells like they're doing a everyday task?

Well, then I hope one day that treatment will become cheap enough so it can benefit everybody.

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The immune system is thought to already clear mutated and defective cells as part of their everyday activity.

Cancers which grow to a detectable/dangerous population have to find some way to evade this immune surveillance and hitting off switches like "immune checkpoints" is one way to accomplish this. So, blocking the off switches helps the immune system resume its everyday task of killing weird cells.

Is this envisioned as a treatment for detected cancer, or a preventative measure, or is the discovery too recent to tell at this point?

This is already being deployed in therapies today - https://en.wikipedia.org/wiki/Checkpoint_inhibitor

And it works well in conjunction with other therapies that guide or otherwise help the immune system find the cancer. In particular, a style of designer gene therapy just approved by the FDA, of which one is called a Chimeric Antigen Receptor - https://en.wikipedia.org/wiki/Chimeric_antigen_receptor

These are in patients now, and curing people today.

If, for instance, the chimeric receptor (a designed synthetic cell-receptor) is able to enable immune cells to better sense the cancer, and that is coupled with the checkpoint inhibitors to prevent the cancer from disabling those immune cells, one's own immune cells will then be able to directly kill the cancer.

The checkpoint inhibitors (associated with the Nobel here), take the brakes off of the immune system. This can of course be dangerous, but generally one of cancer's first tricks it learns is how to apply those brakes to hide from detection. So by tuning down the sensitivity to the immune system's 'brake pedal', one's own immune system becomes more capable in fighting cancer.

Maybe helpful for the HN crowd: the adaptive immune response typically prioritizes a low false positive rate. A developing cancer sneaks by as a false negative. Checkpoint blockade moves the immune system to a regime of higher sensitivity, at the expense of potentially lower specificity.

Yes, this. The side effects are not to be underestimated (they are similar to autoimmune disorders). Moreover, there are no good tests yet that can predict whether someone will respond. If someone does, it's sometimes spectacular but with all therapies from the field combined optimally, less than 40-50% responds (with single drugs it's around 10% I believe).

From the detailed writeup (https://www.nobelprize.org/uploads/2018/10/advanced-medicine...):

"Inactivation of the Ctla4 gene in mice, performed in the laboratories of Arlene Sharpe and Tak Mak, confirmed and further substantiated its negative regulatory role, since these mice developed very severe autoimmune disease associated with proliferating T cells (Tivol et al., 1995; Waterhouse et al., 1995)."

"In the first-in-man study MDX-010 was given to 9 patients in a phase I clinical trial at a single dose of 3 mg/kg and a response was observed in some melanoma patients (Hodi et al., 2003). The same year complete regression was reported in another trial in some treated melanoma patients, while severe autoimmune side effects were also observed (Phan et al., 2003)."

So I wouldn't take it "just in case" like a daily multivitamin. Plus, monoclonal antibodies are expensive!

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