Normal people have circulating T-cells that have recognized the CALR mutation as an invader to the immune system and destroyed it

[clubdino]

This study has demonstrated that normal people have been exposed to the CALR mutation but their immune system recognized the enemy and destroyed it.

The study was first done on Jak2 positive people since patients with double mutations (Jak2 and CALR positive) are very rare. They noticed that the Jak2 positive people had circulating T-cells that recognized the CALR mutation and destroyed it. From there the scientists studied T-cells in the normal population and noticed they also had circulating T-cells that had a memory in regards to the CALR mutation and their immune systems recognized it as an invader.

For some reason our immune system didn't recognize the troublemaker and said, "take your shoes off and stay awhile." This research was done by the same group who are trying to develop a CALR vaccine. Interesting stuff.

ncbi.nlm.nih.gov/pmc/articl...

[mhos61]

Thanks, will have a look over the weekend. All very interesting.

[welshhuw]

Thank you for posting this information, I have been following the CALR phase I vaccine study that is currently underway in Denmark, hopefully there will be some positive results when the study concludes.

[clubdino in reply to welshhuw]

It's very interesting indeed. I always assumed the CALR mutation was only found in people with MPNs. I did not know that healthy people had been exposed to CALR but their immune system took appropriate action. Even people who are JAK2 positive fought off the CALR mutation.

[welshhuw in reply to clubdino]

I also wasn't aware until I came across this abstract about 6 months ago.(ncbi.nlm.nih.gov/pubmed/286... Then doing a bit more research I also came across the CALR phase I vaccine study currently being performed at the Harlev hospital in Denmark (Primary end date Feb 2020 but not sure when they will report). If the study had been performed in the UK I would have been very tempted to volunteer. The in-vitro data looks very compelling, particularly considering that the T-cells were able to recognise several epitopes and were cytotoxic to autologous CALRmut cells. If the research group can develop a vaccine to stimulate a sufficiently strong specific immune response, things could get very exciting. Fingers crossed !

[clubdino in reply to welshhuw]

I'd love to see a bunch of dead degranulated CALRmut cells laying all over the place and then their tiny bodies are phagocytized by the biggest, fattest, hungriest macrophage that ever existed. We'll call him Fat Albert. It would make my day.

But seriously, wouldn't it be awesome to take part in the clinical trial and have a place in history in the destruction of the CALR mutation. I have high hopes for this one.

[welshhuw in reply to clubdino]

hahaha !..... what a wonderful description ! Here's to Fat Albert, the hungriest CALRmut macrophage ever to have existed !

[socrates_8 in reply to clubdino]

Hey Clubdino...

Yes, I agree quite an interesting finding indeed. I shall watch this one continue to unfold with an increased level of interest.

Thank you for the Post

Steven

(Sydney)

[clubdino in reply to socrates_8]

It could be the beginning of the end. 💥💥💥💥

[socrates_8 in reply to clubdino]

Yes, I agree that there is every reason to be a tad optimistic but still a ways to go yet...

Cheers

Steven

[welshhuw in reply to clubdino]

I suspect you may already have the link to the CALR vaccine study but just in case

clinicaltrials.gov/ct2/show...

[clubdino in reply to welshhuw]

I was actually looking at it right when you sent it. Where is the study taking place? In Denmark or the US?

[clubdino in reply to clubdino]

Ah, nevermind, it looks like it's Denmark.

[welshhuw in reply to clubdino]

At the Herlev Hospital in Denmark, it's a small phase 1 study, recruitment is closed, so I'm assuming they already have the numbers. This group is very active in researching the immunogenicity aspects of MPNs, I believe they are also looking into the feasibility of a JAK2 vaccine but it seems much more challenging from an immunological perspective.

[clubdino in reply to welshhuw]

We are lucky to have scientists that are interested in our disease. I used to be a veterinary oncology technician and I was tasked to give the melanoma vaccines to the dogs. Melanoma in dogs is a very aggressive and ugly cancer...it almost always grows in the back of the mouth (and smells like the bog of eternal stench) and it usually metastasizes to the lungs very rapidly. I can't say that the vaccine was super effective so I hope the CALR vaccine pulls through and delivers. Melanoma moves much more rapidly then ET so we are lucky in that aspect. I think there is a lymphoma vaccine too.

[Hidden]

The T-cells do not rid the body of the genetic mutation but only the cells produced as a result of the mutation.

[clubdino in reply to Hidden]

As long as in the future my ADHD T-cells can develop a memory and recognize the cancer cells as unwanted houseguests I will take what I can get.

[Wyebird]

Amazing I look forward to reading it. Thank you so much