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Author Topic: New technique for bioengineering stem cells shows promise in HIV resistance  (Read 442 times)

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Offline Zoob626

  • Member
  • Posts: 20
Hello everyone
New technique for bioengineering stem cells shows promise in HIV resistance
UC Davis research paves the way for human clinical trials using gene therapy
Using modified human stem cells, a team of UC Davis scientists has developed an improved gene therapy strategy that in animal models shows promise as a functional cure for the human immunodeficiency virus (HIV) that causes AIDS.  The achievement, which involves an improved technique to purify populations of HIV-resistant stem cells, opens the door for human clinical trials that were recently approved by the U.S. Food and Drug Administration.

The artikel here
http://m.ucdmc.ucdavis.edu/publish/news/newsroom/9583

Offline Hoyland

  • Member
  • Posts: 81
Wow, a 94% stem cell purity achieved. This is absolutely amazing.

The team's HIV treatment is very similar to that used by the City of Hope. In their clinical trial back in 2010, the CoH team found that the treated stem cells prevailed in the body but they could not get a high enough percentage of the modified cell into patients to make the treatment efficacious. I think their purity was about 18%.

Calimmune's transduction rate won't be known until the results of the current trial are announced but the rate will be nowhere near 94%.

If these results translate into efficacy in the trial that is about to get under way, then this research will represent a monumental step forward in the application of genetic technology in the race to find a cure for HIV.

Offline Matts

  • Member
  • Posts: 234
This is pretty interesting; a genetic triple therapy against HIV: TRIM5alpha,CCR5 shRNA and a Transactivation Response Element decoy. The mice got CCR5 and CXCR4 viruses and are still healthy 6 months later :)

http://onlinelibrary.wiley.com/doi/10.1002/stem.1919/abstract

Quote
Abstract


The successful suppression of HIV in the “Berlin Patient” has highlighted the ability of HIV-resistant hematopoietic stem cells to offer a potential functional cure for HIV infected patients. HIV stem cell gene therapy can mimic this result by genetically modifying a patient's own cells with anti-HIV genes. Previous attempts of HIV gene therapy have been hampered by a low percentage of transplanted HIV-resistant cells which has led to minimal clinical efficacy. In our current study, we have evaluated the in vitro and in vivo safety and efficacy of a tCD25 pre-selective anti-HIV lentiviral vector in human hematopoietic stem cells. This pre-selective vector allows us to purify vector transduced cells prior to transplantation so an increased percentage of gene modified cells can be delivered. Here we demonstrate the safety of this strategy with successful engraftment and multi-lineage hematopoiesis of transduced cells in a humanized NOD-RAG1-/-IL2rγ-/- knockout mouse model. Efficacy was also demonstrated with significant protection from HIV-1 infection including maintenance of human CD4+ cell levels and a decrease in HIV-1 plasma viremia. Collectively, these results establish the utility of this HIV stem cell gene therapy strategy and bring it closer to providing a functional cure for HIV infected patients. This article is protected by copyright. All rights reserved

Preintegration HIV-1 Inhibition by a Combination Lentiviral Vector Containing a Chimeric TRIM5α Protein, a CCR5 shRNA, and a TAR Decoy
http://www.nature.com/mt/journal/v17/n12/full/mt2009187a.html
« Last Edit: December 23, 2014, 10:54:52 AM by Matts »
triumeq

Offline Jmarksto

  • Member
  • Posts: 534
Wow...a stem cell "Hat Trick"!


The speed of stem cell research is VERY impressive...
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
02/25/14 CD4   792/37%  VL UD
07/09/14 CD4 1004/39%   VL UD
11/03/14 CD4   711/34%   VL UD

Offline Zoob626

  • Member
  • Posts: 20
but this is in the beginning right ??
How long it will take to start on human trial !?

Offline Hoyland

  • Member
  • Posts: 81
Quote
but this is in the beginning right ??
How long it will take to start on human trial !?

This research has been going on for about ten years and so it is well beyond the beginning.

The FDA has already approved the trial and so the only thing missing is the funding. It may well be that the CIRM funds the first phase of this clinical trial, who knows? Once funding has been secured, the actual clinical phase of the research can start shortly thereafter.

CIRM funded Calimmune and Sangamo are both trying to achieve something similar to the UC Davis team but a treatment purity of 90+% would put this research ahead of the pack if they can translate this work into the clinic. For this reason alone it would be worth another investment.

I would expect the trial to start some time in 2015 with the first enrolment to be for HIV/Lymphoma patients - same as the CoH trial.

Offline buginme2

  • Member
  • Posts: 3,297
Still doesn't really answer the question of even if it theoretically worked who on earth is going to line up for a stem cell transplant??  Unless you have cancer that's failed chemo no one is going to be prescribed this.  I don't want end stage cancer. Do you?  There is a real chance of dying getting a stem cell transplant.

Don't be fancy, just get dancey

Offline Hoyland

  • Member
  • Posts: 81
The stem cells will be harvested from the patient i.e., their own stem cells will modified and returned to them. This is no different to the Calimmune and Sangamo trials. While it is impossible to be one hundred percent certain that there will be no adverse events associated with this treatment, the pre-clinical work looks good from that perspective.

Offline Cosmicdancer

  • Member
  • Posts: 155
The article about this research doesn't mention if this technique required chemotherapy or some form of ablation therapy to destroy the immune system before reintroducing the modified stem cells.  It would be helpful if they would describe the process more fully.  Ideally, a milder form of chemo, or not at all, can be developed to make this technique feasible on a wide scale basis. 
Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable
May, 2014 - undetectable, 784 cd4, 48%
October, 2014 - UD, 1084 cd4, 48%

Offline Matts

  • Member
  • Posts: 234
a clinical study is planned for 2016 in Berlin.
The researchers want to publish more information soon.
The procedure will be similar to UC Davis. I read nothing about a chemo, I think that it wont be necessary anymore. Next year we will know more :)

triumeq

 


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