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Zinc Finger Proteins Put Personalized HIV Therapy Within Reach

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Tadeys:
I guess Im having link problems today... :P

http://www.rttnews.com/2235392/sangamo-biosciences-presents-clinical-data-from-sb-728-t-hiv-studies.aspx?type=ct

sfpvguy41:
Here's how I summarize this great news on HIV: Sangamo today announced further progress from actual clinical trials on the path to a functional cure of HIV (disease controlled without needing meds).... "the data that have been generated in the course of the clinical investigation of this novel therapy on reductions in viral load and the levels of viral reservoir, as well as the increases in total CD4 cells, demonstrate that a single SB-728-T treatment has the unique ability to enable sustained immunological functional control of HIV in the absence of ART."

Essentially they have announced that by pretreating with an existing drug, Cytoxan (which knocks out CD4s), they have learned how to engraft enough modified CD4 cells to modify the immune system sufficiently in certain types of patients (CCR5 heterozygotes) so it can stave off HIV without needing meds, similar to how the Berlin patient was cured. Now they have to prove this in other cases using higher engraftments, and it will have to go through Phase 3 trials and come to market, so it's not something we'll see available for years.

There's a lot to this announcement, but it's a positive step. 

dico:
This thread was very interesting. Unfortunately it wasn't updated since December. Any news about this Sangamo trial and comparison with Calimmune ?

I want to restart this topic and know your thoughts (especially Hoyland).

I think there are 2 advanced approaches (clinical trials) as of 2014 :
- Sangamo/City of Hope with ZFN and cytoxan (for both CD4 and HSC) : beginning in 2014
- Calimmune/Benitech with ddRNAi and busulfan (for both CD4 and HSC) : beginning in 2014 too (with buslfan)

Why are these approaches important ? As the vaccine approach failed during the past 30 years. There is not a single vaccine nor a drug that have cured even a single patient. So, if one of the two above approaches succeeds, we can hope to have a functional cure for a subset of patients in less than 10 years.

The subset of patients are, I think, healthy youngs with no other disease (no HBV / HCV) and treated early for at least 2 years (i.e. with the lowest viral reservoirs) and with documented low viral set points (less than 5000 copies/ml ?). This subsent of patients are clearly a minority but what is important is that afterwards, the technique can be improved to cure others (like me as I have been late diagnosed and had at the beginning a high viral set point of more than 10,000 copies/ml).

I am more optimistic with the Calimmune trial as it has shown a higher engraftment of biallelic-modified CD4 according to studies and they have cleverly added an antifusion protein (C46).

I think it is possible to combine the Calimmune/Benitech method with that of Prof Ben Berkhout (inhibiting HIV proviral replication) and with a combination of Busulfan for HSC and Cytoxan for the CD4. I think both chimio will raise the engraftment to a maximum level of one third modified cells (which is not that high unfortunately) at the beginning and maybe more afterwards as the non-modified CD4 will die with treatment interruption.

So what are your thoughts ?

Hoyland:
Dico,

There is a third trial approved but not yet recruiting.

Busulfan and Gene Therapy After Frontline Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma
http://www.clinicaltrials.gov/ct2/show/NCT01961063?term=city+AND+hope+AND+HIV&rank=3

The City of Hope clinical data from four years ago and the Sangamo clinical data are the only data available for these gene therapies in humans. The Calimmune pre-clinical data is very positive (one more pre-clinical publication to be released) but it is pre-clinical and therefore cannot be compared directly with the other two data sets. The Calimmune science looks good but, until we see some data coming out of the trail, I think it is too early to judge which of these approaches is likely to be the most efficacious.

I understand that Calimmune is already planning a second trial, which is a good sign that they are confident the results for this trial will be positive. The other thing about Calimmune is that they are not a government or educational facility nor do they have other treatments in the pipeline. Curing HIV is there entire raison d'etre. A failure for them is the end of the line and so I am sure their scientists are paddling like crazy to make Cal-1 work, or at least work out how to refine it so that it does work.

Hoyland:
I should have added that the lead scientists or CEO for all of these trials are attending this roundtable event. Dr Zaia for Sangamo/CoH, Dr deGiusto CoH and Mr Breton Calimmune.

http://www.oxbridgebiotech.com/events/gene-therapy-risky-business/

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