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Galena Biopharma, Inc. Message Board

  • bensjaca bensjaca Sep 10, 2013 3:50 PM Flag

    Lacking logic???

    would like to know more before I invest. Adam Feuerstein report does make sense. Why would NeuVax which is supposed to train T-cell to target Her2 expressing tumor cells and kill them NOT work in tumors that have high expression levels for HER2??? This is a big question still unanswered by Gale. I know we all should hope that a good vaccine comes out for breast cancer but I doubt given the lack of clear scientific explanation that this is it. They chose to compare group with low Her2 expression to controls but remember that the group with low Her2 expression might also be the one with low recurrence with/without NeuVax? So the Phase 2 results are not clearly scientifically valid. Why is the rate of recurrence not significant among those that had high her2 expression? if they can clearly explain that then yes we should put high hopes on this one. Otherwise it might just turn out to be a big SCAM. Pls note I am not a short. Have never shorted any stocks in my life. If somebody can point out something they know that would support the efficacy of this one please do so here.

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    • Actually as Dan mentions this was addressed by Dr. Peoples. He said:

      "The basic biology between HER2 0-2+ vs 3+ has been well-documented, and we use this distinction clinically when we subtype breast cancers. 3+ tumors are more aggressive/dangerous. We have shown that vaccines work best in less aggressive tumors.

      The immune system can become tolerized against large quantities of antigen. More is not always better (contrary to the argument). We have shown an element of tolerance in the T cells from HER2 3+ patients relative to the T cells in lower expressors.

      HER2 is sufficiently immunogenic that even the lower levels of HER2 expression can be recognized by highly-specific, vaccine-induced T cells. These CTL can recognize and destroy tumor cells with low and intermediate expression levels (hundreds of papers demonstrating this concept because there are actually only a couple of HER2 over-expressing cell lines available for experimentation. The vast majority of all of the lab work has been done on low- and intermediate-expressors).

      Most importantly, one of the documented differences in the 3+ tumors, and probably related to their aggressiveness, is that these tumors down-regulate HLA expression, making themselves "invisible" to the immune system. Rolf Kiessling at the Karolinska Institute, Stockholm has written extensively about this phenomena. We are currently trying to verify whether Herceptin treatment can restore the HLA expression, explaining our observation that the CTL-eliciting vaccines, such as NeuVax, may be useful in the 3+ patients in combination with Herceptin."

      There was also a study out of UPenn looking at these kinds of vaccines which concluded:

      "By logistic regression analysis, we also found that subjects with higher prevaccine HER-2/neu expression appeared less likely to respond to immunization."

      They conclude that as the level of Her-2 expression increases the response to the vaccine decreases.

      //Deaux

      • 1 Reply to deauxh
      • OK I agree. Let us assume as deauxh and danindenver pointed out that due to rapid turnover with HER3+ type tumors CTLs are not able to do their killing fast enough to stop recurrence. What would be interesting to know in this case is what is the comparison of the recurrence rates between the HER1&2+ group unvaccinated versus HER1&2 vaccinated. I thought the results compared low HER vaccinated group with the general group which had high HER expression profiles also. If the recurrence rates of the low HER expression group is low to start with, why vaccinate them?

        Sentiment: Buy

    • Ben: I'm going to give you a non-scientific response and (later, not at this time) then will track back through some of what had previously been provided by Galena's scientific board (I believe it was Dr Peoples) who have documented the scientific answer to your inquiry. First, please understand the "generation time" for atypical cells Varies Considerably! With HER2, the most aggressive atypical cells are classified as 3+ ("HER2 Pos") while the HER2 1+ and HER2 2+ expressions are NOT considered HER2 Positive, but rather classified as atypical cells that express Low to Moderate levels of HER2. Back to cell "generation time:" What AF refuses to acknowledge and to discuss (in simple terms) is that HER2 3+ cells Very Aggressive, & their generation rate is more rapid than the rate at which the body produces T-cells. ALSO, keep in mind that Regardless the body's T-cell numbers, if those T-cells are not "oriented " (trained) to recognize an atypical cell as an antagonistic element (a destructive factor), then no matter how many T-cells supported or produced by a specific "body," there will not exist sufficient impetus for those (untrained) T-cells to launch an effective cytotoxic battle against the destructive atypical cells. NeuVax serves the role of an effective catalyst in "training" large numbers of one's own T-cells to "search and destroy" the HER2-expressing atypical cells. HOWEVER, at the 3+ (HER2 Pos) levels, and although aided by an increased number of "Trained T-cells," the body's immune system is not able to overcome the rapid generation-time of the atypical cells. There's also a finite limit to the numbers of T-cells that can be stimulated to be developed (regardless the quantity of GM-CSF) by the body. Finally, on a personal note, I have been witness to the ravages of HER2 3+ and let me assure you that those atypical HER2, 3+ cells generate at hundreds of times the rate at which, for example, some of the slow-poke atypical prostate cancers progress!

    • Think you stated the dilemna quite well....I came to the same conclusion after reviewing the node negative vs node positive data.

 
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