Cancer Immune Therapy for MPN

[EPguy]

There is a post from Manouche about an actual trial related to the subject here.

healthunlocked.com/mpnvoice...

The article here has some technical details on the subject, if anyone finds interesting I noted some items.

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

We have "neo-antigens", which arise from acquired somatic mutations in cancer cells.

Neo antigens usually are too varied to target easily <<However, in MPN, there is no such need to target personal neo-antigens as 80–90% of patients harbor either the JAK2V617F or CALR mutations. Additionally, we recently reported that the immune system can selectively target cells carrying the JAK2V617F and CALR exon 9 mutations>>

Real action <<we have finalized a phase I clinical vaccination trial with a CALR-mutant epitope for patients with CALR-mutant MPN>>

Basis for the trial posted by Manouche <<Therapeutic cancer vaccination against the JAK2V617F and CALR exon 9 driver mutations is likely to induce immune responses. However, the immune dysregulation in MPN could potentially prevent tumor-specific immune responses and negate any clinical effect of vaccines. As such, targeting regulatory mechanisms in the tumor microenvironment may also be important>>

Checkpoint inhibitors seem not promising for MF (pubmed.ncbi.nlm.nih.gov/343... while << Patients with non-advanced MPN (e.g., ET) have stronger and more frequent responses compared to patients with advanced MPN (e.g., PMF)>>

The trial in Manouche's post <<As the expression of the cornerstone immunoregulatory proteins PD-L1 and ARG1 is increased in MPN, we speculate that vaccination against both of these will enhance the anti-tumor immune response in patients, and we have consequently launched a phase I/II clinical vaccination trial with PD-L1- and ARG1-derived epitopes in patients with MPN>>

I often mention INF + something being a path fwd <<Given the biological effects of IFN-α, the combination of IFN-α with vaccination seems logical>>

[EmeraldA]

Hi, thanks for posting about this ( to you and Manouch). It is interesting reading. My take away from this - if I have this right is that there is a away to differentiate between Jak2 normal cells and mutated which can then be targeted. This has been an issue previously. Also, it mentions using therapies in conjuction with one and other. A concept that is being repeated more and frequently. There is hope!

[EPguy in reply to EmeraldA]

Agree on the general idea. My understanding greatly simplified is CALR has a more direct route to therapy since it is more easily identified in the body. Note they are doing CALR first: <<we have finalized a phase I clinical vaccination trial with a CALR-mutant epitope for patients with CALR-mutant MPN>>

So I think it's likely any breakthroughs will happen there first. But ways to "out" jak2 are under way so there should be progress to come using some of the same new methods.

[gvibes]

Thanks for sharing information- always interesting. Hey just curious. When you reference and link the papers, some have Pub Med or Google Scholar (abstracts) or PMC free article (whole article). Is there a way to get full articles from pub med or google scholar outside of joining these things?appreciate it

[EPguy in reply to gvibes]

I'm in front of the same paywalls. Occasionally I find a work around thru enough creative searching and I post the link to the full reports. Otherwise I do have a friend who can access university docs, but I ask only for the most extreme wants.

[gvibes in reply to EPguy]

It seems that the journal's keep rights and require subscriptions - each journal somehow separate. sometimes there seems to be free access - maybe government money helped fund research or authors somehow released them to the public. I'll ask my doc who is a researcher next time we meet. It would be nice if they gave free access to patients - people with the disease. thanks for all your sharing of information....

[Manouche]

The anti-tumor immune response is a key factor for success, but studies also suggest that baseline tumor burden, or tumor size, predicts response to immunotherapy. It makes sense that the immune system will be more successful fighting a lower tumor burden if it wants to avoid exhaustion on the long run. That’s why a low allele burden and therefore a state of minimal residual disease could have an impact on the outcome.

[EPguy in reply to Manouche]

According to this idea (baseline tumor size) it could be they will try to get high alleles lower via INF before starting some of the new therapies.

[Manouche]

That’s precisely one of the aim of interferon therapy.