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Inovio Pharmaceuticals, Inc. Message Board

  • regrose58 regrose58 Mar 13, 2014 5:20 PM Flag

    Posgost....Just trying to get my head around this hTERT thing.

    I have no scientific or medical background, so bear with me. 85% of cancers have expression of hTERT mutation (i.e. fraying of the ends of some portion of their DNA I suppose) Targeting of hTERT directly, would cause a fatal form of anemia (if I understand correctly) INO's hTERT vaccine does not directly target hTERT per se, but boosts cancer killing T-cells by 18 fold over whatever is 2nd best. Hope I am getting this right. Now a big question I have is does cervical cancer express hTERT mutation? If it does, wouldn't the hTERT vaccine be effective against it? I know that breast, lung, prostate and melanoma do express hTERT mutation. Tell me how it is that if the hTERT vaccine is effective in all these cancers, that it is not (for lack of a better word) redundant.

    Sentiment: Strong Buy

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    • Good question regrose! One for Bernie I guess!

      Sentiment: Strong Buy

    • Hi Regrose58,
      From VGX-3100 phase I result and multiple discoveries from INO. Can you able to predict the result of VGX-3100 phase II result?

      Sentiment: Strong Buy

    • Regrose- I pulled up my thread where Daddy asked a question about the hTERT vaccine. I gave a very detailed explanation there. But to answer your question here:
      1) hTERT is either upregulated (increased protein expression), or has an activating mutation causing increased activity, or can actually downregulated in ~85% of tumors. Most of these tumors have either up regulation or an activating mutation.
      2) Just because it is upregulated or activated does not mean it is doing anything for tumor progression
      3) For Cervical cancer: Cervical cancer is caused by oncogenic proteins present in high risk HPV strains. These proteins cause cell cycle and checkpoint proteins in the host cells to proliferate, regardless of external signals (usually external signals like growth factors are required for them to proliferate). They cause cells to proliferate, and when they proliferate uncontrolled, they acquire mutations which lead to the development of immortalized cells and hence cancers. hTERT may or may not be mutated in cervical cancer, but the cause of the cervical cancer is the infection with HPV. Whether hTERT is mutated or not does not matter for the development of cervical cancer as cervical cancer would develop whether hTERT is mutated or not.

      4) Here's where it matters. If you have an hTERT mutation in cervical cancer, and the mutant hTERT is being expressed (mutated protein is being produced), then that protein can still be targeted by a vaccine to help cure the cervical cancer (even if it is not the cause of the cancer). If the mutated hTERT protein is not being expressed, or if the hTERT protein is normal (not mutated) then you really can't target it, because the vaccine wouldn't work (if the protein isn't being expressed by the cancer cells- T cells won't recognize the cancer. If the protein is normal/not mutated, you don't want to target it because you may cause autoimmunity to hTERT expressing cells, causing bone marrow failure.

      Hope this helps.

    • visceraljunket@bellsouth.net visceraljunket Mar 13, 2014 6:06 PM Flag

      Regrose58, I stayed in a Holiday Inn express but I can't answer you very well written question. With your permission and give you as the question author, I would like to copy this post over to Postgost's thread so he will more likely see it.

      Sentiment: Strong Buy

 
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