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Author Topic: Citi of Hope RNAi / Gene Therapy trial  (Read 2658 times)

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Offline freewillie99

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Citi of Hope RNAi / Gene Therapy trial
« on: December 08, 2008, 04:58:59 PM »
Hmmm...it will be interesting to hear more...

HIV-Resistant Stem Cells Engrafted to Treat AIDS-Related Lymphoma

Melbourne, Dec 8, 2008 (ABN Newswire) - Leading developer of RNA interference (RNAi)-based therapeutics Benitec Limited (ASX:BLT)(PINK:BNIKF) announced today that Dr Amrita Krishnan, had presented a poster on the human HIV trial at the American Society of Hematology conference held in San Francisco CA USA.

Dr Krishnan is the principal clinical investigator of the pilot study being undertaken at City of Hope in Duarte, California. The presentation was entitled "First in Human Engraftment of Anti-HIV Lentiviral Vector Gene Modified CD43+ Peripheral Blood Progenitor Cells in the Treatment of AIDS Related Lymphoma (ARL)".

This pilot feasibility study is supported through a collaboration between Benitec and City of Hope and is Benitec's first human trial. The trial uses a triple therapy delivered using a lentiviral vector developed at City of Hope. The rHIV7-shl-TAR-CCR5RZ vector suppresses HIV by expressing three nucleic acids that are directed against key steps in HIV replication.

The study transplanted autologous (patient derived) blood stem cells which were genetically modified using the lentivirus vector into four AIDS patients with lymphoma who first received high doses of chemotherapy. The study showed that cells engrafted in all four patients, that new blood cells expressed the anti-HIV RNA, and there were no complications.

"We have shown that we can deliver gene modified cells which have the potential to limit the HIV infection. If we can continue to develop this approach and successfully apply it to other AIDS patients, then genetic therapy for HIV could become a reality", said Dr Krishnan.

"We are very encouraged by these initial findings. This is an extremely important trial as it is the first human clinical trial with expressed RNA interference trigger (shRNA) and the first triple gene therapy combination trial for HIV/AIDS. It is the also the first human trial for AIDS using hematopoietic stem cells (HSCs) transduced with lentiviral vectors" said Sue MacLeman, Chief Executive Officer, Benitec Limited.

The Study

The study with City of Hope is entitled, "A pilot study of the safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentiviral vector-encoding multiple anti-HIV RNA's."

The pilot study is designed to determine the safety and feasibility of RNA-based anti-HIV therapy with lentivirus-transduced hematopoietic progenitor cells (HPC) in patients undergoing autologous hematopoietic stem cell transplantation (HCT) for intermediate and high grade AIDS lymphoma.

The lentivirus vector encodes three forms of anti-HIV RNA: RNAi in the form of a short hairpin RNA (shRNA) targeted to an exon in HIV-1 tat/rev (shI), a decoy for the HIV TAT-reactive element (TAR), and a ribozyme that targets the host cell CCR5 chemokine receptor (CCR5RZ). The vector, used to transduce autologous CD34-selected HPC, is called rHIV7-shI-TAR-CCR5RZ and was manufactured by the Center for Biomedicine and Genetics at City of Hope.

Following standard mobilization of HPC and collection by apheresis (HPC-A), a portion of the cells were cryo-preserved and left unmanipulated for later use as treatment. The remaining portions of the cells were enriched for CD34+ cells, cryo-preserved, and later genetically modified by infection with rHIV7-shI-TAR-CCR5RZ.

The subjects underwent conditioning therapy and at the time of autologous HCT, the rHIV7-shI-TAR-CCR5RZ transduced cells were infused, followed 24-hrs later by the infusion of untransduced autologous HPC-A.

More info:

NEW YORK DEC 08, 2008 (Reuters Health) - Anti-HIV genes can be introduced into autologous peripheral blood progenitor cells, resulting in a potentially HIV-resistant treatment for AIDS-related lymphoma (ARL), according to study findings presented Sunday at the American Society of Hematology annual meeting in San Francisco.

"We are the first study to incorporate multiple genes into hematopoietic stem cells collected from the patient for the treatment of their HIV infection," lead author Dr. Amrita Krishnan told Reuters Health. "In addition, we are the first to use a lentiviral vector for the transfer of the genes into the stem cells for AIDS and, even more importantly, this is the first in-human use of this mechanism of using a short-hairpin RNA trigger for RNA interference in any disease."

Autologous stem cell transplantation is viable treatment for relapsed or high risk ARL. Although treatment-related mortality in ARL patients is comparable to that seen in HIV-negative lymphoma patients, optimal outcomes are hampered by the presence of HIV.

Highly active antiretroviral therapy can achieve undetectable HIV levels in the blood, but HIV tissue reservoirs and resistance to HAART may still impair outcomes. These issues, however, could be circumvented if it were possible to make the stem cells intrinsically resistant to HIV.

To do that, Dr. Krishnan, from the City of Hope National Medical Center, Duarte, California, and colleagues used a lentiviral vector to incorporate short hairpin RNA to HIV tat/rev, a nucleolar localizing TAR decoy sequence, and a ribozyme targeted to CCR5 into the peripheral blood progenitor cells of four patients with ARL.

The results indicate that following high-dose chemotherapy, stable engraftment of these autologous, anti-HIV cells was possible. No serious adverse events were noted.

Dr. Krishnan said that further research is needed to examine how to improve engraftment and whether engraftment of cells with less intensive non-marrow-ablative doses of chemotherapy is possible, "which would then allow the use of this procedure in HIV-infected patients without lymphoma."

Beware Romanians bearing strange gifts

Offline HALOO

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  • Posts: 60
Re: Citi of Hope RNAi / Gene Therapy trial
« Reply #1 on: December 09, 2008, 01:31:25 PM »
Wow! really need to hear more if this cell are really resistant to HIV.
V.Interesting :o

Offline freewillie99

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  • Posts: 312
Re: Citi of Hope RNAi / Gene Therapy trial
« Reply #2 on: December 09, 2008, 03:23:45 PM »
This is a useful presentation as well.

[attachment deleted by admin]
Beware Romanians bearing strange gifts

Offline HALOO

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  • Posts: 60
Re: Citi of Hope RNAi / Gene Therapy trial
« Reply #3 on: December 09, 2008, 03:54:52 PM »
freewillie99

file is not working

Offline sensual1973

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  • Posts: 196
Re: Citi of Hope RNAi / Gene Therapy trial
« Reply #4 on: January 31, 2009, 10:57:56 AM »
that is really uplifting. How long this is going to take ? and how do i get updates about it ? went to the city of hope site but no details being posted regarding progress  in this study.
God grant me the serenity to accept the things i can not change.

Offline freewillie99

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  • Posts: 312
Re: Citi of Hope RNAi / Gene Therapy trial
« Reply #5 on: January 31, 2009, 03:55:53 PM »
I'm in touch with one of the primary HIV docs at City of Hope and progress is ongoing.  As far as how long this is going to take, your guess is as good as mine pretty much, but safe to say it won't be next week.  I will say this: the people I've discussed this with are very optimistic there's merit to this approach and it's not going to just go away.

Whenever I learn something new or come across new info on the work being done at City of Hope, I'll post it.
Beware Romanians bearing strange gifts

Offline sensual1973

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  • Posts: 196
Re: Citi of Hope RNAi / Gene Therapy trial
« Reply #6 on: January 31, 2009, 04:33:18 PM »
thanks freewillie for the feed back and i just hope that this study is not just another bluff.finger crossed.
God grant me the serenity to accept the things i can not change.



 


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