tag:blogger.com,1999:blog-6235733697979948062.post990464479158804200..comments2024-03-19T00:33:30.191-07:00Comments on our brain tumor cocktails and stories: Peptide Vaccine for 5 year old with GBMStephen Whttp://www.blogger.com/profile/00777652648990108253noreply@blogger.comBlogger7125tag:blogger.com,1999:blog-6235733697979948062.post-44312864614560343132016-10-27T06:49:14.423-07:002016-10-27T06:49:14.423-07:00Immunotherapy is at best at minimal residual disea...Immunotherapy is at best at minimal residual disease. One can fear that there are still some silenct glioma cancer stem cells residing that will restart growing at a certain time point. These cells are not sensible to chemo- nor radiotherapy. Immunotherapy can still target them. There are some publications in the internet on immunotherapy for children with malignant glioma. Geiger JD et al. Cancer Res 2001;61:8513, Ardon H et al. Pediatr Blood Cancer 2010;545:519. So there is experience with tumor lysate pulsed DCs. The Pittsburg group generated results in children on vaccinations with peptides as well. The proposed approach for defining tumor-specific peptides by comparing tumor material with healthy material is a well known strategy of current research for vaccines in adults. Early clinical experiences show feasibility without major toxicity. In part with this methodology one escapes to the MHC restriction of most classical defined peptide vaccines. As this is a known immunology and immunotherapy methodology my guess is that this methodology can in theory also be applied to children. Administration to a child will be under the condition of "Individuelles Heilversuch". SVGhttps://www.blogger.com/profile/06622761974790805847noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-55132086954535492252016-10-21T13:53:38.780-07:002016-10-21T13:53:38.780-07:00I'd be happy to look at the molecular patholog...I'd be happy to look at the molecular pathology results and give a shot a interpretation. My email address is on the User Information page, at the top of the blog.Stephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-56656342071127974382016-10-21T13:17:51.053-07:002016-10-21T13:17:51.053-07:00Thanks for the clarification. You're quite ri...Thanks for the clarification. You're quite right about Optune, I hadn't thought of that when I raised it as a hypothetical example. <br />Really, this is an example of how children can't be treated as if they were just small adults.SteveMDFPhttps://www.blogger.com/profile/02023680327735781469noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-16336113111369560692016-10-21T13:12:24.971-07:002016-10-21T13:12:24.971-07:00Just a quick comment on Optune; you won't be p...Just a quick comment on Optune; you won't be permitted to use it as it's not approved for people below 21 years of age. This is because it affects fast growing cell, which a child has in his/her brain naturally as the brain is still growing.<br /><br />That is has NED is wonderful. I agree with everything that Steve has said in proceeding cautiously and judiciously. <br /><br />All the best, this is a beast at any age but certainly more so for a child.Logan Lohttps://www.blogger.com/profile/05539011850820749278noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-75441513650394986052016-10-21T11:42:30.932-07:002016-10-21T11:42:30.932-07:00Winston,
This is a devastating, terrifying disease...Winston,<br />This is a devastating, terrifying disease, and the challenge is all the more magnified when the afflicted is a child.<br /><br />My own feeling is that a clinic offering an unapproved therapy should be viewed skeptically.<br /><br />A clinic that offers a treatment they've never tried on a child before should be viewed *very* skeptically.<br /><br />A clinic that suggests treating a young child as if he/she were just a small adult should not be trusted at all. Pediatric care is a specialty for a reason. Young children are not simply small adults, not biologically, not psychologically, not in terms of treatment systems or approaches needed.<br /><br />Your situation is both enviable and especially challenging. With no measurable tumor present any more, you can never know if *any* intervention is responsible for delaying/preventing relapse, or if somehow an intervention might have paradoxically hastened progression.<br /><br />As long as this remains the situation, I might suggest limiting interventions to ones that are low risk, low-impact, relatively reliable, and affordable.<br /><br />Perhaps focusing on allowing your child to live a relatively normal, happy childhood may be prudent. So something like an Optune helmet might *biologically* be a wonderful intervention, but might be a dreadful burden on a child who might (or might not) actually benefit from it.<br /><br />Meanwhile, a "methylated" tumor, generally, is known to be relatively responsive to radiation and temozolomide. Continuing with standard treatment protocols may be prudent.<br /><br />I'm a big believer in participating in well-designed clinical trials. My own wife is receiving nivolumab/OpDivo in a trial, and gets to stay on it (protocol permitting) indefinitely, at zero cost to us. Hard to beat something like that.<br /><br />Of course, almost any trial of interest won't admit her unless there is measurable tumor to gauge progress--that is, she might not qualify until new tumor tissue is detected (though not necessarily so in all trials).<br /><br />So, I'd recommend studying the available pediatric GBM trials at<br />https://clinicaltrials.gov/ct2/results?term=pediatric+glioblastoma&recr=Open<br /><br />You might sort out which ones seems most promising (perhaps only to use when relapse is detected) and review these options with your oncologist (and/or folks here). That way, if and when that dreadful day happens, you might be prepared with a plan already in place.<br /><br />Meanwhile, low-risk interventions that aren't a massive burden on anyone seems reasonable. I might suggest curcumin and mushroom extracts (PSP/PSK, etc) as benign additions. Many others are worth considering. Clicking on terms in the column on the right will yield many potentially valuable leads.<br /><br />Best wishes,<br /><br />SteveSteveMDFPhttps://www.blogger.com/profile/02023680327735781469noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-35195697493308890432016-10-21T08:55:57.474-07:002016-10-21T08:55:57.474-07:00Stephen-
Thanks for your quick response.
In revi...Stephen-<br /><br />Thanks for your quick response.<br /><br />In reviewing the sequencing documents we have seen (difficult to interpret!) we don't see the mutations you reference but that doesn't mean they are not there. The German Whole Exhome sequencing may reveal more.<br /><br />The description I pasted is from some PDFs they sent us as part of becoming enrolled in their compassionate use vaccine program.<br /><br />I'll take a look at the link you sent but that sounds reassuring.<br /><br />Thanks again<br />WinstonWinstonhttps://www.blogger.com/profile/15705192975084247031noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-63307831006038180212016-10-20T08:59:31.660-07:002016-10-20T08:59:31.660-07:00Hi Winston, and welcome.
I'd be interested to ...Hi Winston, and welcome.<br />I'd be interested to know more about the results of the genetic testing, as pediatric gliomas typically have a different genetic and epigenetic background vs. adult gliomas. Specifically was there mutation detected in histone 3.3 [H3F3A], or ATRX mutation? p53 mutation?<br /><br />I feel that looking at vaccines at this time is indeed logical. Vaccines are typically more effective when there is minimal residual tumor, as an actively growing tumor puts out immunosuppressive cytokines that makes any effective anti-tumor immune response less likely.<br /><br />I'm curious where you found this description of the CeGaT vaccine approach. I've heard through word of mouth that this company has created vaccines for patients on a Compassionate Use basis, but there is no information on their website about it that I can see. The company seems to be more about diagnostics than treatment.<br /><br />I'm not sure that peptide vaccination in pediatric patients would bring up any different issues versus other types of vaccines (such as tumor lysate-pulsed dendritic cell vaccines). There is some information on SL-701, a peptide vaccine, in pediatric glioma:<br /><br />"Peptide-based vaccination has been well tolerated in children with<br />gliomas, with no > Grade 3 non-CNS toxicities."<br /><br />http://www.stemline.com/ScientifcPresDownloads/SL-701_AACR%202012_Poster.pdfStephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.com