Using T-Cells To Fight MPN - CALR And JAK2 Vaccine

[PVReporter]

Being developed by the Danish team at Copenhagen University hospital. Professor Mads Hald Anderson was my contact and the project lead.

The good folks in the ET group alerted me to this research and tagged me about interpretation in "laymen's terms." It's a long study and written at the Phd level. Stay with me this is a Long post, but well worth reading.

Here are the questions I posed:

1 - Can you provide an update in laymen’s terms on your exciting research?

2- Would this provide a preventative measure against developing an MPN, but also a potential cure for those already effected?

3 - At what stage is your research? Any details you can provide would be greatly appreciated.

Here is the email from Professor Anderson (mostly unedited) -

Thanks for your mail. It is great to hear that our research is generating interest. We also believe that our results the last couple of years in the MPN field is highly interesting and potentially can get huge impact on the future treatment of MPN.

Let’s start with CalR – we have described that the immune system is able to recognize and react towards the mutated C-terminus of the CalR protein – thereby killing the mutated cells. We have seen spontaneous immunity in patients. What we also saw was that patients later in the disease (MF) seem to have a weaker response compared to ET patients - which suggest that the neoplastic cells escape the immune system. We hope that we will be able to restore and increase the immune responses towards the CALR mutation by vaccination and have started the first clincial vaccination trial - a phase I with 10 patients where we of cause mainly look at safety (but in reality (as there appear to be no safety issues) will look if vaccination can do something with the disease). Depending on the results (which we will have already later this year) we will know if we have to do more (i.e. do more immune activation than just this vaccine - that could be a combi with other forms of vaccines, antibodies or something else) and, in the little longer perspective, if we can start vaccination even before people have MPN –you could indeed imagine that we will be able to vaccinate healthy individuals to prevent (or decrease the likelihood) of MPN

The jak2 mutation is a bit different and more difficult. We have seen that the immune system recognize and can react towards neoplastic cells due to a reaction towards this mutation. However, this is more difficult for the immune system, partly because the mutation is only in 1 amino acid (which basically means that there is less novel for the immune system to react against compared to healthy cells). This does not mean that a Jak2 vaccination is not possible, and we hope we at some point can include this, but this is not how we are starting in patients carrying this mutation (which is most as you know). In has been described that the JAK2 mutation up regulates another protein called PDL1 on neoplastic cells. We have shown that the immune system also can react towards PDL1, and we plan to start a vaccination trial in the patients with a Jak2 mutation against PDL1 later this year (hopefully before summer – we are sending the protocol to the authorities very soon, but you never know how long time these things take – especially since we are a University Hospital Center with limited resources). Again we will have to wait to see if this does something good in the patients and then we will have to modify from there. What is extra interesting with this form of vaccine is that we will target not only the neoplastic cells but also the parts of the immune system, which are bad for anti-cancer immunotherapy (the part of the immune system that is defined as the regulating immune system which is preventing anti-cancer immune response). So we might even combine this PD-L1 based vaccine with the CalR vaccine in CalR mutated patients.

So in short, our findings that the immune system are able to specifically react towards MPN cells will, in my mind, make it possible to more specifically target the neoplastic cells in patients in the future. We are already trying to translate these findings into clinical trials, and, hopefully, this will be followed by other centers as there are many other means of utilizing these findings. I am also trying to generate interest from the Industry, as we need this, if we really want to develop this into something real for patients.

Here is the original research article - bit.ly/2EqJZxi

Hope you enjoyed this cutting edge research report!

Cheers,

David - PV Reporter

[1466]

Amazing, thank you for your research! It will help so many from the worrying and sadness that comes from gene mutations!

[mhos61]

Thanks for keeping us up to date, sounds promising.

[Rachelthepotter]

Thanks, David. Looks there might be a way of sorting out the defective JAK2 mutation eventually - but not tomorrow.

RAchel

[Innessant]

Thank you so much for sharing this. It is encouraging that work continues even though these diseases are very rare.

[Mica11]

Encouraging reading David. Thank you!

[Cando67]

Thank you for this .It offers hope and is encouraging to know that progress is ongoing

[Anag]

Dear David! This is indeed a bit of breaking news! I am CALR and I’ve always known the the imm system has a lot to do with this and I’ve have been doing everything possible since 10/2017 to free up my body from all environmental toxins possible and give my imm system a chance to fight this on its own. This encourages me to continue my soft by consistent battle. I even make my own shampoo and cleaning products. There is no doubt a difference in my physical and emotional health. I’m not keen on vaccines (my daughter was vaccine damaged) but I believe this is very specific, different from virus vaccines. If something is found for CALR, JAK2, etc. will probably be around the corner. Thank you so much for writing the university and for informing us!! I will watch the development closely!! 🙂

[OZland]

Thank you David!

Great news for all of us even though historical progression from Phase 1 to phase 3 and then Pharma help $ and approvals from regulators may take 5 to 10 years.

Still am wondering if you or anyone knows whether to continue with annual flu shots since it has been proven that our immune system is already compromised.

Thanks again

[WileyFrench in reply to OZland]

I thought it’s recommended that we definitely get the flu shot. And in Canada, to get the shingles vaccination too as it’s not a live virus here.

[socrates_8]

Hey David...

Thank you for this update regarding possible future MPN remedies...

This seems to hold a certain amount of promise, and naturally, it will be worth watching for all future developments etc...

Thanks for sharing this and the links to the original article too...

Steve

(Sydney)

[Kinsale]

Thanks so much David. It’s great to see that research such as this is taking place.

Mark

[PVReporter]

Wow, I'm blown away by your kind replies, thank you so much! One of my goals with PV Reporter is to research new treatments, medical devices and procedures, to make life easier (or more promising) for MPN patients.

Best,

David

[Bluetop]

Thanks David, this is very interesting and great that you got it straight from the research team.

[PVReporter in reply to Bluetop]

Thank you Bluetop.

[Bluetop]

P.S. David,

Now I'm going to be really cheeky. I wondered if you had heard any news about the Nutrient trial which was started in 2017.

curetoday.com/articles/inve...

The results were expected out by now, but recent discussions on this forum suggest they have not been published yet. Any suggestions?

[PVReporter]

Yes, that is a bit cheeky...lol, but a good question. I will put out a feeler and see if I can get any info. In the meantime, here is an article from MD Anderson on foods that can reduce inflammation. Be sure to check with you MPN specialist, ex. - grapefruit is not allowed with Jakafi - bit.ly/2UDByWc

[welshhuw]

Hi David, I just wondered if you have received any updates on this interesting vaccine research ? Best regards, Huw

[PVReporter in reply to welshhuw]

Hello Huw, I have not received any updates on the vaccine research....although I have inquired. Hopefully there will be an update before too long.

Best,

David

[Mpncoda]

Thank you so much for this info and May we all be blessed with new scientific research and a potential cure!

[PVReporter]

Sure glad to get the word out. There are more clinical trials in MPN now than ever. That's a good sign.