City of Hope Clinical Trial

[Hoyland]

I think this trial

http://www.clinicaltrials.gov/ct2/show/NCT01961063?term=city+AND+hope+AND+HIV&rank=3

has just been granted $1.5M by the NIH. This should add to the private donations already received and may be sufficient for CoH to start recruiting.

[dico]

I have more hope with the Calimmune trial.
Studies in monkeys have shown higher levels of engraftment of bi-allelic modified CD4 with Calimmune.

[Hoyland]

Dico, I would not be so dismissive of this research. The new trial is building on the previous Pl safety trial which was conducted in 2010. Since the conclusion of that trial the team at the CoH has been working on ways to improve the transduction rate as it was too low in the first trial. I have not seen any recent data but if they are ready to go with a new trial then one would have to think that they have made a substantial improvement.

[Hoyland]

http://breakthroughs.cityofhope.org/rossi-grant-hiv/12322

Just some more background info.

[dico]

Thanks. Always good to hear from you Hoyland.

But I must add that we should not pin our hope in such trials. They will fail as the Sangamo did and as the previous CoH phase I did. According to monkey studies, the Calimmune trial will have a better outcome but even if it shows some success, it will not cure by itself. Without vaccine, there will not be any functional cure.

Right now Philipp Johnson has a clinical trial in London called antibody passive gene transfer. Although both the vector (AAV1) and the Ab (PG9) are outdated, it is the first to begin a phase I clinical trial. Soon an improved version with a more potent antibody (VRC07) will be tested in California called VIP. We are hopefully very close to a cure.

[Hoyland]

Dr Rossi's team at the City of Hope may have found the increase in efficiency that they were searching for. In their latest paper they describe their use of stem cells (same as Calimmune but with a different target) and how to attack the HIV with rnai. They conclude:

"In summary, combinatorial gene therapy approaches are often most effective when targeting multiple stages of viral replication. We present here the improved MCM7 platform with enhanced flexibility, increased safety with sufficient level of transgene expression for long-term inhibition of HIV in HSPC-derived macrophages. We demonstrate that more is not always better but rather a balance between transgene expression, mechanism of action, and target choice is required for optimizing the combinatorial approach. With the improvement in vector efficacy and strategies to increase the frequency of HIV-resistant cells, we hope to achieve sufficient gene marking and antiviral potency to move closer to a functional cure of HIV."

http://www.nature.com/mt/journal/vaop/ncurrent/full/mt201432a.html

This is great news and, as the current trial uses blood stems cells as the shrna vector, we may be able to assume that the new efficiency will manifest in the data from this trial. This research, IMO, represents a significant step forward in the use of gene therapy for the treatment of HIV.