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Biotech / Medical : Oncothyreon -- Ignore unavailable to you. Want to Upgrade?

To: Nonos who wrote (2275)	8/25/2013 7:45:35 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 2344

Jim: Cyclophosphamide... don't know. I'd say that it looks obvious in 2013, but not when START got off ground? It was such a difficult trial to run, I think that Merck's personnel are heroes and that the vision of Merck's executives is pretty cool. Glad someone took this shot, after reviewing the preclinical stuff (including some from Red et al.). So, regardless of which direction the vaccine takes now? A huge thanks is due to everyone who contributed to this regal study. Tregs.... Guffaw. If you look at my original post, that's exactly the point where I said (paraphrasing) "something happens". :-) I don't understand either, but I'm interested in what is known about relative timing of chemo to radiation and effects on T cell subsets. Also interested in any info re. chemo alone, effects on Treg. Don't know this stuff. Dr. Butts has to be all over that, as Merck would be. That's why I'm interested in the sCRT group, for what it might tell us. Thanks again. Rick

To: Nonos who wrote (2275)	8/25/2013 7:54:02 PM
From: Nonos	Read Replies (2) \| Respond to of 2344

Rick and the author of the following study bring up the possibility that the positive survival effects of some of the subgroups in START could have been solely from cyclophosphomide. ncbi.nlm.nih.gov!po=87.0370 “CPA lacks any significant activity in NSCLC [18], and the dose used in this setting is below that used in cytotoxic chemotherapy, it is unknown whether any of the observed antitumor effects following L-BLP25 therapy can be attributed to the immunomodulatory effects of CPA.” I feel that the CPA given pre vaccination has some effect on overall efficay because of its synergistic effect in combo with a therapeutic vaccine but it is unlikely the CPA is soley responsible for efficacy because this retrospective study showed cyclophosphomide to have very little therapeutic activity in nsclc. ncbi.nlm.nih.gov But in the same study (albeit an mouse study at UC Davis) it was found that ncbi.nlm.nih.gov!po=87.0370 “In the present preclinical study, we showed a rather modest antitumor response, which is consistent with the primary endpoint result of the phase III trial. However, only the publication of the detailed results of the phase III trial will allow further comparisons and conclusions between patients or subgroups of patients and this preclinical model.” SIDE NOTE: I do not think a 41% decrease in tumor foci in the mice is a “modest” antitumor response! This study does highlight the need for a longer term dose of l-blp-25 as in the group of mice which had only undergone 2 months of vaccinations there was no difference in the number of tumor foci between tx and non tx whereas after the second two month regimen was there the 41% difference between the two groups. CPA alone in the two cycle group did experience a 24% reduction in tumor foci as did the l-blp-25 only group compared to the no tx group.. CAUTION. This is an animal study with a small n. However, this study if it were valid to compare to humans suggests l-blp-25 needs to be administered for up to 10 months before therapeutic results are seen, that a second dose of cyclophosphamide is a good idea (as it lessons the Treg count) and that the combination of cyclophosphamide and l-blp-25 works best even though CPA alone in mice does have some efficacy in decreasing induced adenomas in mice.