Calimmune: Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-

[geobee]

http://m.bizjournals.com/sanfrancisco/blog/biotech/2015/03/hiv-aids-cirm-stem-cells-sangamo-sgmo-usc.html?r=full

FDA said Ok to stem cell trial.

[tryingtostay]

http://m.bizjournals.com/sanfrancisco/blog/biotech/2015/03/hiv-aids-cirm-stem-cells-sangamo-sgmo-usc.html?r=full

FDA said Ok to stem cell trial.

Does this only address the CD4 cells?  Aren't there the macrophages and other cells HIV infects?

[Hoyland]

The theory is that Hematopoietic Progenitor/Stem Cells (HSC) proliferate and  differentiate into a wide variety of blood cells and so genetic modifications at the progenitor/stem cell level get passed on to daughter cells of various types. This includes CD4 cells and macrophages.

This is why both Calimmune and Sangamo are targeting these HSC cells. They represent the greatest coverage of modified cell types from a single infusion.

[tryingtostay]

The theory is that Hematopoietic Progenitor/Stem Cells (HSC) proliferate and  differentiate into a wide variety of blood cells and so genetic modifications at the progenitor/stem cell level get passed on to daughter cells of various types. This includes CD4 cells and macrophages.

This is why both Calimmune and Sangamo are targeting these HSC cells. They represent the greatest coverage of modified cell types from a single infusion.

Thanks Hoyland

[Hoyland]

In a National Cancer Institute sponsored trial, the Fred Hutchinson Cancer Research Center in Seattle will use Calimmune's Cal-1 to treat AIDS patients that have Lymphoma. The trial will start in April.

https://www.clinicaltrials.gov/ct2/show/NCT02378922

[xman]

the biggest problem to overcome is that hiv could adapt itself to the modified immune system by using the other coreceptor to enter the cell. i must admit that i'm very skeptic about this approach. the risk is to fail after several years of testing.

[tryingtostay]

the biggest problem to overcome is that hiv could adapt itself to the modified immune system by using the other coreceptor to enter the cell. i must admit that i'm very skeptic about this approach. the risk is to fail after several years of testing.

Aren't they including the cxcr4 receptor also???  That's a big oversight.  Is the cxcr4 receptor even studied???

[Hoyland]

CXCR4 tropic patients are excluded from the current trial but Calimmune is researching how to target this strain of HIV. The company is going to start another clinical trial in Australia in a few months time. It is possible that the new trial will include both CCR5 and CXCR4 tropic patients. No details of the trial have been released.

[POZnLA]

Is there any one who has participated in the first 2 cohorts of the study.? I almost was in the first one and I am trying again for the 3rd. I just went off Meds.

[Hoyland]

POZnLA, those on the trial will be bound by a non-disclosure agreement and so, publicly at least, they will not be able to say much.

Meanwhile, Calimmune continues to publish pre-clinical data supporting its treatment.

http://www.nature.com/mtna/journal/v4/n4/full/mtna201510a.html

Ex vivo challenge experiments with splenocytes from the treatment group displayed protection from both R5-tropic and X4-tropic HIV-1 infection, with inhibition of HIV-1 replication as measured by p24 ELISA of culture supernatant.Twelve weeks after human CD34+ HSPC transplantation, high-dose intravenous infection of R5-tropic HIV-1 exists. Treatment group animals maintained CD4+ T-cell levels and reduced viral loads within the peripheral blood and lymphoid tissues. Interestingly, the treatment group of animals displayed background levels of HIV-1 detection within the peripheral blood and lymphoid tissues tested at 14 weeks postinfection. The lack of substantial evidence of HIV-1 detection within the treatment group suggests that LVsh5/C46-modified cells were able to systemically control the infection or potentially completely inhibit the initial viral challenge infection. Furthermore, LVsh5/C46 gene-marking and transgene expression was stable up to 6 months post-transplantation of transduced CD34+ HSPC, and a reporter version of the construct was able to demonstrate significant downregulation of CCR5 in vector-modified cells in vivo.