Hi all,
I'm 54 from Scotland, diagnosed in August with over 90% resection and am on my last stretch of radio/chemo before starting TMZ 5/28 for 6 months in December.
I'm currently in the position of deciding if i should start TTF therapy alongside maintenance, undergo DC&NDV vaccine at IOZK with maintenance, or embark on all three at once?
Any thoughts would be very much appreciated as i hear evidence for both TTF and DC treatments working well with TMZ, i just don't know if it would be wise to combine them all. If that is the case, which would be more 'worth' it? If TTF doesn't work well with dexamethasone due to its immunosuppressive effects would it be better to support the immune system with the DC vax first?
Thank you for any thoughts on this matter, i aim to join you all and get my cocktail up soon!
Mark
Hi Mark
ReplyDeleteI'm sorry I don't have answers only more questions..are you being treated within the NHS? My husband is 45 and on an almost identical timescale to you. I feel we keep banging our heads against a brick wall as the only answer is "follow the programme and see how you are after the 6 months TMZ". Were you able to have tumour tissue stored correctly for DC Vax? Is your clinician more open minded about additional treatments?
I do recognise that but we just went ahead with all our research and are implementing what we believe is safe. The vaccination route we gave our oncologist all the details and as the tissue is yours you can ask for it to be transferred and on the basis of the company writing to my oncologist that is not an issue for her. I also requested all the pathology reports and scan reports. I would say that the NHS staff have to work within strict protocols but my experience is if you ask and persist then you will get somewhere. What you will not get is information volunteered. Let me know how you get on. Mark
DeleteI think that there were probably no clinical trials so far which combined vaccines with TTF to know if it is good combination or not. So far my observation is that the more stuff you combine is the better and there were very few combination approaches that gave worse outcome than single things. It looks to me that the more you combine the better. But this is just my observation of a person without much knowledge. Iozk is not the only one clinic offering vaccines. The vaccines at iozk are more expensive than unifontis for example. I can't say about the efficacy of each. Unifontis does not offer dendric cell vaccines but manipulates tumor tissue instead if you have a tumor tissue.If you don't have a tumor tissue then unifontis offers personalized peptide vacccine which has the most peptides of all the clinicks. Unifontis has the newcastle virus too.
ReplyDeleteWhat dose of dexamethasone are you on? The study showed interference of dexamethasone with TTF only at a dex dose over 4 mg per day.
ReplyDeleteOne of the authors of that study, Ken Swanson, gave a presentation at the SNO 2014 conference in Miami, saying that NovoTTF worked partially through immunogenic cell death. I would expect that it would work well combined with a vaccine.
It seems to me that treating this aggressively upfront with a multi-modal approach would be superior to the sequential approach that is more commonly used (ie wait until progression until moving on to the next therapy). NovoTTF plus vaccine therapy has not yet been tried, but intuitively I would prefer the triple combination therapy, if it's within your means.
I already pasted this comment from Dr. Van Gool (who appears to be well known in immunotherapy):
ReplyDelete"immunotherapy does not induce tolerance to other treatment modalities later-on. On the contrary: it has been shown that immunotherapy targets e.g. TRP2 taking out TRP2 expressing tumor cells (TRP2 is a resistance mechanism against temozolomide)."
TRP-2 is one of many possible antigens used in a peptide vaccine. It is one of the six used in the ICT-107 vaccine.
DeleteAre these other 6 antigens known? Or if I ask otherwise...can you get the same vaccine at german clinic as you would get in a clinical trial (for example ICT-107 or DCVax) ? If peptides used are known then I assume they can make same vaccine?
ReplyDeleteI was told that german clinics have thousands of peptides to choose from. Hallwang offers 50-200 peptides. If you want to spend more money they might give you more, but you would have to pay extra. They told me some of the bestones they have are survivin, muc,wlm or something like that. I did not ask unifontis which peptides they have but they told me that they can give me as many as I like. Both those clinics don't do dendric cell vaccines but peptide vaccines instead which are simpler and cheaper to manufacture and can be stored. Immune-therapy does dendric cell vaccine which is primed with up to 5 peptides only for one or 2 HLA types. Unifontis and Hallwang have peptides for all HLA types. Unifontis was recommended to my by storemytumor.com as best value for the money. In unifontis they have two different peptide vaccines one cheaper where they match the peptides only to HLA type and another peptide plus where they match it to both HLA type and tumors molecular markers.
DeleteHi Anna & Stephen,
DeleteDo you think that autologous vaccine, to the extent there is a tissue available to prepare it, taken in Van Gool's' clinic at IOZK, would be a better clinical choice than a peptide-based vaccine at Unifontis or Hallwang? (putting the costs of treatment aside).
The six antigens included in the ICT-107 vaccine are AIM-2, MAGE-1, TRP-2, gp100, HER-2, and IL13Ra2. In each case, only a small snippet of the protein is used (that is basically what a peptide is - a small piece of a protein).
ReplyDeleteBut the MAGE-1 and AIM-2 peptides in this case are HLA-A1 restricted while the others are HLA-A2 restricted. You would have to be tested for HLA-A subtype before choosing which peptides to use.
The ICT-107 trial was restricted to patients positive for HLA-A1 or HLA-A2. But in fact, only the HLA-A2 positive patients seemed to benefit from the vaccine, so the two HLA-A1 specific antigens probably weren't that important in the patient outcomes.
I'm sure the clinics in Germany could synthesize these same peptides used in the ICT-107 vaccine, but that would only be useful if the patient is HLA-A2 positive. Also, these peptides are pulsed onto dendritic cells to make the ICT-107 vaccine.
The important thing is that the clinics need to match the peptides according to the patient's HLA-A serotype.
DCVax is very different from ICT-107. They are both dendritic cell vaccines, but DCVax is made using lysate from the patient's tumor, while ICT-107 doesn't require any tumor tissue - the dendritic cells are just pulsed with synthetic peptides.
DeleteSo to clarify - you get the same quality if you go to clinical trial (for example ICT-107) or to one of the german clinics that use the same peptides ?
DeleteAlso, what is the exact protocol in choosing the peptides? Do they examine the tumor tissue and then select the peptides or "the more the marrier" ?
You could probably get something similar, but I wouldn't say "the same". ICT probably has its own proprietary methods for making the vaccine, and every lab would do things somewhat differently.
DeleteI think with the German clinics you get what you pay for. As Anna pointed out, at Unifontis they match the peptides to the patient's HLA type, and for an extra few thousand Euros they will also match the peptides to the genetic profile of the tumor.
At Hallwang they select the peptides based on analysis of the paraffin-embedded tumor tissue, or 20 unstained tumor slides.
At unifontis they told me to bring the paraffin block too. So somehow they work both with the molecular report and the paraffin block. I was told that Prof. Dreves was a head of Hallwang in the past before he opened Unifontis and that he "pioneered" some of the methods how those vaccines are made. What I am concerned is the adjuvents they use.I did not ask them what adjuvents they use at unifontis. I read some studies that in the past peptide vaccines were produced with some adjuvents which were causing them to be less effective. I hope that they are up to date with this recent research, but there isn't to many other options.
DeleteDo you think that autologous vaccine, to the extent there is a tissue available to prepare it, taken in Van Gool's' clinic at IOZK, would be a better clinical choice than a peptide-based vaccine at Unifontis or Hallwang? (putting the costs of treatment aside).
DeleteI was told that whole tumor vaccine made from fresh/ frozen tumor tissue is better than peptide vaccine. IOZK whole tumor vaccines are dendric cell vaccines and unifontis is whole tumor vaccine which is probably not a dendric cell vaccine. I don't know if dendric cell whole tumor is better or worse than the unifontis whole tumor vaccine. Dendric vaccine you can probably make more effective by doing the tetanus preconditioning with it. I don't know if such preconditioning would be of any help with unifontis whole tumor vaccine. So there are lots of variables here. Maybe storemytumor.com can give more info.
ReplyDeleteInformation on Dr. Hans Bojar and NextGen Oncology group in Dusseldorf Germany added to the "German immunotherapy clinics" document in the Brain Tumor Library.
ReplyDeletehttp://www.prof-bojar.de/en/