We have a tumor tissue and it is preserved alive. I am thinking what should we do with it now. Unifontis makes vaccine with manipulated whole tumor tissue and they don't perform leukapheresis. Iozk makes dendritic cell vaccine with it and adds newcastle virus to it. Dr. Nesselhuts dendritic cell vaccine is so much cheaper. I am wondering how all those compare.
I have the same good question Anna! In the end...I think we are going to follow our guts.
ReplyDeleteHey guys, I am also really interested in immunotherapy, but neurosurgeon is against it because I had supratotal resection of low grade oligodendroglioma. I will ask him why he is against it, since I don't see any negative side effects (except high costs and sometimes people get fewer at time of vaccination).
ReplyDeleteAnyway, lets clear the terminology first. I think the "whole tumor vaccine" as you call it anna is also dendritic cell (DC) vaccine. As far as I understand you have dendritic cell vaccine from whole tumor lysate/tissue, and peptide dendritic cell vaccine. The difference is that peptide dendritic cell vaccines is loaded with premade peptides, so it "arms the immune system" to fight against these antigens/markers. The problem is that brain tumors are really heterogenous, so glioblastoma from 2 different people doesn't neccessarily have same markers. Also we only know a portion of most common tumor markers, there may be 1000 more we don't know about. Because peptides can be premade in laboratory in bigger quantites these vaccines are cheaper (like at Dr. Nesselhuts).
The other vaccine is "whole tumor lysate" dendritic cell vaccine. As far as I understand they load the dendritic cells with the patient's tumor tissue (and all its known and unknown markers). In theory the immune system should then search and destroy all the tumor cells. Therefore it should be more effective than peptide vaccine. In theory that should prevent "tumor escape" - destroying all the tumor cells (with known and unknown tumor markers/antigens). Making of "whole tumor lysate" DC vaccine is personalized, so therefor more expensive, time-consumin and should be more effective.
As far as I understand the immunotherapy (with DC vaccines) should be most effective with minimal tumor burden and with fresh tumor tissue (so as soon as possible after surgery), because the remaining tumor cells which aren't removed with surgery can acquire more/new mutations really fast (especially in GBM), so the immune system boosted with DC vaccine doesn't "search&destroy" for these new mutations.
Immunotherapy approach already has really good results (long-term survivors), but only on fraction of patiets (I think around 10%-20%) - check Linda Liau's video, where she speaks about people surviving 10 and more years with no GBM tumor reccurrence. So as far as I understand they are now working on achieving these results on more/all patient.
This is my understanding of immunotherapy approaches, I don't know if I am 100% right so someone please correct me if I'm wrong.
Anyway, my honest opinion - if I had GBM I would try to get "whole tumor lysate" DC vaccine with "immune checkpoint inhibitor" at IOZK & NDV, but price really is higher. And I would do that as soon as possible with fresh tumor tissue.
Hi Matjas, if Im not wrong in Dr Nesselhuts Clinic they also have DC vaccines primed with tumor material not only peptides. Im in contact with them, planning travel in March maybe but first we need to recover her WCB counts, she is around 1.4.
DeleteOh, I thought they only have peptide DC vaccines. Please let us know. But I do think IOZK is the only clinic offering checkpoing inhibitors
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ReplyDeleteI always thought that "whole tumor vaccine" is "dendritic cell vaccine primed with whole tumor lysate", so I am really sorry about misinformation then. If somebody is maybe in contact with any of those clinics it might be worth asking what is the difference in comparison with dendritic cell whole tumor lysate vaccine.
ReplyDeleteMaybe Stephen knows :) ?
As Francisco said, in the end we will probably have to follow our guts
I just got into a 'Dendritic Cell' (DC) clinical trial at the Mayo Clinic in MN. They filtered out my white blood cells to get the DC's but they are using a "standard GBM tumor" to "target" them. I asked why they weren't using my GBM for "targeting". They said that is because they would have to have performed the resection there at Mayo, at the proper time, in order to do that. I shut up at that point because I was glad to be in any immunotherapy trial, but isn't it still possible to use tumor that was preserved in formalin?
ReplyDeleteYou can use that tumor in 2 ways. You can make a vaccine at dr.Nesselhuts clinick in Germany but I was told that it will not be a very good vaccine because the protein in the formalin block are degraded. Other way you can use this tumor you can make a peptide vaccine with hundreds of peptides at unifontis or at hallwang clinicks and you can use this tumor to do the surface testing on it and match the peptides to the surface markers of the tumor in the paraffin block. The price at unifontis for such vaccine with a few hundred of peptides (I don't have the exact number) is about 23 tys euro for 5-6 shots spaced one week apart or so. So it depends what are your funds. You can also ask the doctor to add checkpoint inhibitor to the vaccine. You would have to ask those clinics if they would like you to do the genetic testing on the tumor somewhere else or if they only do the surface antigen testing at their clinics. Oncodepth does the genetic testing of the tumor and methylation status for about 4000tys dollars. So I don't know if it is cheaper to do it there or to do it at the clinics.
ReplyDeleteThe pros of the unifontis vaccine is that you go to Germany once only and you can take the remaining few vaccines home if the laws of your country permit it. With dendritic cell vaccines you can not take them home.
What I understood about the peptide vaccines is that if there were 2 vaccines with the same number of peptides and one was a dendritic cell vaccine and the other one was just a peptide vaccine (which you can store at home) then the dendritic peptide vaccine would be better .But there are no clinics which would offer dendritic cell vaccine with large umber of peptids . Dr Nesselhut has only 5 peptides and only for one hla type. On the other hand unifontis and hallwang have hundreds of peptides and for all hla types so even though their vaccines are not dendritic cell vaccines then they are probably better than dendritic cell vaccine with just a few peptides.
DeleteI called storemytumor to give me some info about the whole tumor vaccines at different clinics. Here is what they told me. Unifontis uses whole tumor vaccines which are not dendritic cell vaccines. They say that those vaccines are suppose to be equally effective or better as dendritic cell vaccines(?) They follow the approach which has been used by the university of pannsylvania for breast cancer vaccine. They use adjuvents most likely montanide or some otherone. They use repeated freezing and thawing. They say that this approach is better than dr.Nesselhuts or the clinic in caribbean because I think that dr. Nesselhut kills the tumor tissue and does not use the freeze thawing. (I don't have any opinions yet)
ReplyDeleteTwo recent review articles which might be useful in making a decision as to which immunotherapy to choose:
ReplyDeletehttp://journal.frontiersin.org/article/10.3389/fonc.2015.00098/full#h5
http://journal.frontiersin.org/article/10.3389/fonc.2015.00012/full
Hello everyone,
ReplyDeleteI am hoping to shed some light on the differences in these approaches. Dendritic cells are cells that gather molecules called antigens either produced exclusively by tumors (by mutations etc) or over-represented on their surface. For vaccines, dendritic cells are isolated from patients. The most well-proven vaccines are those that have used dendritic cells primed with tumor tissue (the fresher the tissue, the better). This is supported by data from DC-Vax (Northwest Biotherapeutics). Tumor cells cannot be fixed in formalin as is standard.
Because fixation is standard, peptide-primed dendritic cells are the next-best options. There is some intriguing data surrounding them, but they are not as well-proven as lysate vaccines. For this approach, it would be crucial that the tumor is covered on their list of pre-generated peptides. For example, EGFRvIII is potent for gliomas but if the tumor doesn't express it, then the vaccine doe not work.
Last, the direct-peptide or direct-lysate injections. I would say these are the least proven. It is hoped that dendritic cells within the body retain these.
Ultimately, the idea is that these cells show the tumor antigens or peptides to T-cells and that stimulates an immune response against cancer cells.
Combining this approach with immune checkpoint inhibitors is the best hope for many patients. Essentially, the vaccine brings T-cells and inhibitors stimulate their response. It is possible to try this in sequence, vaccine then clinical trial in the US with immune checkpoint inhibitors.
I am surprised that peptide vaccines would cost more than dendritic cell vaccines. The cell processing step is the most expensive. Peptides are cheap but maybe the analysis to customize would be expensive. Immune checkpoint drugs are ~100,000 a year.
1) all these vaccines are dendritic cell vaccines: one stimulates the t-cells outside the body (via a process called apheresis, and thus more expensive) and the other is stimulating the t-cells directly inside the body (via adjuvant)
ReplyDelete2) regarding the question of quality of antigen (target strength)
- Whole tumor is always better than peptide
- starting with the cancer cells alive, and killing them in a specific way is always better than using dead (already frozen) cells, or protein (like Nesselhut's approach)
- for the peptide, Multi peptide is always better. Also personalized peptides is always better, also peptides proven to have induced a positive response AGAINST THE CANCER (as opposed to induced a positive response like any virus would do) is always better
To summarize: whole tumors always better, and when you don't have to tumor, go for personalized multiple peptides (that have been proven to induce an immune response to the cancer)
After reviewing Nesselhut's, IOZK, CTCI (Salvin), northwest bio, and Unifontis, for my wife, I decided on Unifontis, and would take the same decision again if I have to.
Finally, combining these vaccines with Immune checkpoint drugs is an excellent idea , but only for advance patients, not all patients
Sam
Sam,
ReplyDeleteI'm currently doing the same comparison. Could I email you for some questions? My email is vkalle455@gmail.com
Another aspect of this to consider is BBB permeability. In generally immune cells don't cross over well thru an intact BBB. BBB leakage and damage is sort of proportional to tumor grade/aggressiveness. Plus RT damage also increases BBB permeability for some period.
ReplyDeleteSo considering the cost of immunotherapies it would also make sense to investigate any mechanism to increase the ability for the primed immune cells to enter the tumor. Unfortunately all I've seen are related to chemo improvement using drugs like taladafil,verapamil, omeprazole or methods like convection enhanced delivery or ultrasonics. So other than RT, not sure there is anything to aid in vaccines.