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.
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.
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.
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 !
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.
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.
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.
The T-cells do not rid the body of the genetic mutation but only the cells produced as a result of the mutation.
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Question for MPN patients in Canada
High Red Blood counts neg. Jak2 and all mutation tests
Don't know what to do!
