If you had asked me 6 years ago about using gene therapy to fight HIV/AIDS, I would have given you a nice rant about how expensive it is, how non-viable it is in the places that need anti-HIV strategies the most, how dangerous it can be, and I would have been damn offended you even considered it.  Waste of valuable resources.

Flash forward to today… I am actually starting to think its not such a bad idea.

Well, specific kinds of gene therapy for HIV-1 might not be such a bad idea.  One such idea is ‘Chimeric Antigen Receptors‘, or, CARs.  CARs are half laboratory designed antibody (to recognize EXACTLY what your target is), half laboratory designed T-cell receptor signalling domains (designed to be really, REALLY good at killing targets).

When a Cytotoxic T-cell is forced to express a CAR, it should turn into a killing machine– seek and destroy whatever the antibody is designed to recognize.

In the case of HIV-1, this is actually a pretty good idea.  Yes, you could also do gene therapy to force B-cells to make broadly neutralizing antibodies… but to get the virus you would have to have the right antibody at the right place at the right time in the right concentration.  And then, you are targeting virus.  Billions upon billions of targets.

Gene therapy strategies that utilize CARs would be a little different– instead of going after the virus, it goes after the infected cells.  The producers of virus.  Its like, instead of blowing up fighter jets (what antibodies do), CARs blow up the battleship launching the fighter jets.

Seems like a great idea!  But things that look like great ideas can turn into huge freaking trainwrecks, and nowhere is this more apparent than with gene therapy trials.

But a group of folks have tried a CAR approach with HIV-1. They tried it 10 years ago.  And their patients are still doing okay:

Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T Cells

They made a CAR that had an outside bit that looked like CD4 (the receptor HIV-1 needs to infect cells) and an inside part that told the infected cells to die– Thus when a Cytotoxic T-cell expressing one of these CARs rolled by an HIV-1 infected cell, its ‘pseudo CD4′ would interact with the Envelope present on the surface of the infected cell, then the CTL ‘persuaded the infected cell to commit suicide.  This was all accomplished via a retroviral gene therapy vector (DANGER! DANGER WILL ROBINSON!)

No, not ‘DANGER!’  A lot have things have changed since those first gene therapy trials.

Whether the experimental strategy  actually worked to treat the individuals HIV-1, I dont know.  But the paper they just published demonstrated that the approach they used is safe.  If the approach is safe, then we can always fine tune what the CAR recognizes on the outside.  We can always fine tune the CTL activation signals that go on in the inside.

The approach used to seem ‘absurd’, but if it works, if we can find an ‘absurd’ approach that works… we can work with that.  Eliminating HIV-1 might require a lot of ‘absurd’ ideas being implemented…

Comments

  1. #1 Optimus Primate
    United States
    May 25, 2012

    YARGH, I hate paywalls.

  2. #2 ERV
    May 25, 2012

    Me too :( I want to link folks to stuff they can read.

    Though honestly, you arent missing much– shorter paper: ‘thank you jesus, we didnt kill anyone trying this’.

  3. #3 charles soper
    London
    May 26, 2012

    Gene therapy used to be the catch phrase to attract easy sponsorship money esp in cancer 15 years ago, but it’s good to see more and more examples of where it does or might work. After all aren’t ERVs sometime original gene therapists?

  4. #4 mo (one of Abbie's elk)
    May 26, 2012

    “Subscription Status

    We do not have a current subscription for your institution for this item in our system; please contact your librarian. ”

    Holy shit, I’m sitting at a pc at a computer pool at a high-prestige German university right now.

  5. #5 nate
    dallas
    May 26, 2012

    this comment is for erv.
    I just wanted you to know it was reading about ervs, some of that reading at your site, that led me to finally admit that humans have common ancestory with primates. I have both a background in engineering and medicine and practice anesthesiology. I grew up immersed in conservative seventh day adventist theology and never seriously studied the scientific basis for evolution. Several years ago I began to read articles and books on evolution and it was obvious that evolution was true however in my mind I held out that even though some genetic markers were know that indicated common ancestory, I thought it still might be possible to have a special creation of man. When the whole picture emerged of thousands of erv markers it was impossible to believe in a special creation or anything for that matter other than common descent. This unlocked my mind and has allowed me to see the entire universe in a whole new way that is quite gratifying. So thank you for all that work that you did at the erv site.

  6. #6 ERV
    May 26, 2012

    *like*

    Really glad you got something from the blog, nate! Just ask if you have any questions!!

  7. #7 Optimus Primate
    May 27, 2012

    *sniffle*

    Welcome, Nate! Hope you stick around!

  8. #8 PONELOPY SILVERDALE MORRIS
    May 27, 2012

    Lets not talk about this lets talk about XMRV again it is addie Sniffs preferred topic. Addie smith is wrong she also rants a LOT.

  9. #9 mo (one of Abbies's elk)
    May 27, 2012

    ERV: Can you send me the paper?

  10. #10 mary (abbie's ilk)
    May 28, 2012

    Yeah Nate.. and Abbie for putting the info out… Not sure about the new look..it’s like a haircut…I gotta get used to it…

  11. #11 tvday
    Texas
    May 28, 2012

    I’m not especially well versed in gene therapy what are the potential drawbacks/problems that might arise from this process? It is great to see that advances are being made especially after the unfortunate events surrounding the Institute of Human Gene Therapy for the University of Pennsylvania. I would be really interested to read this paper!

  12. #12 charles soper
    www.strateias.org/erv.htm
    May 28, 2012

    Having made the opposite pilgrimage, from the despair of irrational materialist futility to theism, Nate, might like to bear in mind that some CERV ‘deletions’ in Orangutans are neatly shared with humans, in a way that at the very least appears problematic for common descent through a putative common ancestor. Whatever your presuppositions, the truth is the only thing that matters.

  13. #13 Poodle Stomper
    May 28, 2012

    Charles,
    Can you post a reference to what it is you are referring to? Maybe we can explain why it isn’t a problem? There are quite a few biologists here, after all.

  14. #14 Poodle Stomper
    May 28, 2012

    (although, I do feel it is worth stating that concluding that a deity must exist because one does not understand a particular phenomenon is called the God in the Gaps fallacy and is an invalid reasoning ;P)

  15. #15 Nate
    dallas
    May 28, 2012

    Charles
    Thanks for the link I will take a look. I agree that it is the search for truth that really matters. That is exactly why faith is not the ultimate virtue. No lost soul could arrive at the “true faith” without a search for truth. This idea invalidates christianity which states that the ultimate virtue is faith, from which you obtain salvation. Logically faith must be a virtue secondary to the search for truth. Sorry for the digression on a science web site.

  16. #16 NS
    May 29, 2012

    Hey ERV fuckface,

    Soon, your mean, contemptible nature will come back to bite you in the ass in ways you didn’t know possible. You too will soon be suffering ME/CFS-like symptoms and will find yourself pleading to doctors who will not listen. And then you will shut the hell up and be humbled by your complete ignorance of your disease. That knowledge of your coming pain is incredibly soothing to me you arrogant and ignorant fuck.

  17. #17 Poodle Stomper
    May 29, 2012

    Hey NS,

    Please learn punctuation. No one here believes that you can affect ERV in such a way as to give her CFS if you can’t even properly use a comma. The knowledge of you slavishly struggling with a copy of “Grammar for Dummies” is incredibly soothing to me.

    Sincerely,
    Poodle Stomper.

  18. #18 Tony Mach
    http://parakoch.blogspot.com/2012/05/is-dr-ruscetti-fraud.html
    June 1, 2012

    They tried it 10 years ago? And it is like totally safe? That makes me a bit uneasy – on religious grounds I refuse to believe in miracle cures that sit on shelves for 10 years.

    Just recently I got spam that went along the lines “Our totally safe miracle cure for all types of cancer has no side effects and was developed decades ago – unfortunately it isn’t approved yet. But we’ll tell you were you can get it anyway.” It came with a long list of favorable studies. (Of course if you get around to poking the favorable studies, they start to smell a bit fishy – kind of Ruscetti studies saying he found XMRV in ME/CFS patients).

    Abbie, have you poked these gene therapy studies?

    Speaking of Ruscetti and poking: I heard he is totally legit and respected researcher. So is his wife. And his former mentor Gallo too. Don’t believe John Crewdson. And please don’t poke Ruscetti.

    After all, bitch fights are much more enjoyable. Alas, I don’t know any crazy female ME/CFS patients who look good. Would be nice to have a bitch fight with bikinis and everybody all oiled up. Much more important than getting the fraudsters that tried to swindle us all. Much more important. And not a stupid diversion at all.

  19. #19 Tony Mach
    June 1, 2012

    Oh, I’ve just see, it has been published in sciencemag – so it must be legit. After all, I heard Dr. Alberts is highly interested in maintaining a quality journal – and not letting science become some tabloid, like some hates say it already is.

  20. #21 Slothrop
    June 9, 2012

    And this one is in human trials now:

    http://scienceblogs.com/erv/2008/07/03/personalized-hiv-therapy-withi/

    With some results:

    http://mobile.reuters.com/article/idUSTRE78I3IP20110919?irpc=932

    Does it now make sense that if they can get this to work as a one time treatment, that could benefit Africa over lifelong ARVs, with possibly less cost?

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