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

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Matts:
Yes he is only a simple hematologist in Heidelberg. I think he gave only his good name for CalImmune for a decent amount of money. :) Don't know what to think about the trial, there is not much information.  Let's see what will happen.

Hoyland:

--- Quote ---there is not much information
--- End quote ---

This is the abstract of a paper that Calimmune will be presenting in two weeks time at the ASGCT conference. I hope this helps.

[48] Engineering Resistance to HIV-1 Infection with a Dual Therapeutic Lentiviral Vector

Bryan P. Burke, Maureen P. Boyd, Michelle L. Millington, Helen Impey, Jane Zhang, Maria V. Carroll, Joanna Camba-Colon, Naomi Keech, Frederic Delebecque, Orit Wolstein, Annett Howe, Rachel Koldej, Tamara Nicolson, Bernard R. Levin, Valerie Rezek, Dimitrios N. Vatakis, Scott G. Kitchen, Louis R. Breton, Jeffrey S. Bartlett, Geoff P. Symonds. Calimmune, Inc., Los Angeles, CA; Division of Hematology-Oncology and UCLA CFAR, The David Geffen School of Medicine, University of California, Los Angeles, CA

We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) capable of generating cellular resistance to multiple strains of both R5- and X4-tropic HIV-1. LVsh5/C46 (Cal-1) has two separate mechanisms of action for inhibiting HIV-1 infection: (1) down-regulation of CCR5 expression via RNAi; and (2) inhibition of HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This combinatorial approach allowed for two points of inhibition for R5-tropic HIV-1 reducing the potential of escape mutations, and was also active against X4-tropic HIV-1. Cal-1 is being clinically developed for use in cell-mediated gene therapeutic applications for treatment of HIV-1 infected patients, for engineering HIV-resistant CD34+ hematopoietic stem/progenitor cells (HSPC) and CD4+ T-cells. Here we report Cal-1 pre-clinical safety and efficacy data for inhibition of HIV-1 infection in vitro and in vivo. Peripheral blood mononuclear cells (PBMCS) and CD4+ T-cell lines treated with Cal-1 were resistant to both clinical isolates and laboratory strains of HIV-1 that were R5-tropic, X4-tropic, or dual-tropic. In addition, Cal-1 modified PBMCs displayed greater protection from HIV-1 infection compared to PBMCs modified with either transgene alone. The ability of Cal-1 modified CD34+ HSPC to confer protection from HIV-1 infection in vivo was determined using the humanized Bone Marrow, Liver, Thymus (BLT) mouse model. Following intravenous challenge with R5-tropic HIV-1, Cal-1 transduced human CD34+ HSPC treated animals demonstrated recovery and maintenance of CD4+ T-cells and significantly reduced viral load compared to control animals that received non-modified human CD34+ HSPC. Four of six animals treated with Cal-1 modified cells had undetectable viremia at terminal analysis, whereas HIV was readily detected in all control animals. Cal-1 modification supported normal hematopoietic development and function without evidence of toxicity. Cal-1 treatment of PBMCs did not induce apoptosis, proliferation, or inflammatory responses; and CD34+ HSPCs treated with Cal-1 displayed normal differentiation, low potential for immortalization in vitro, and oligo-/polyclonal hematopoietic repopulation in vivo. As such, the preliminary safety profile and current efficacy data for Cal-1 strongly support the use of this vector and therapeutic paradigm for clinical treatment of HIV-1 infection.

JazJon:

--- Quote from: Hoyland on April 30, 2013, 09:54:53 PM ---
We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) capable of generating cellular resistance to multiple strains of both R5- and X4-tropic HIV-1.

Peripheral blood mononuclear cells (PBMCS) and CD4+ T-cell lines treated with Cal-1 were resistant to both clinical isolates and laboratory strains of HIV-1 that were R5-tropic, X4-tropic, or dual-tropic.

Four of six animals treated with Cal-1 modified cells had undetectable viremia at terminal analysis, whereas HIV was readily detected in all control animals. Cal-1 modification supported normal hematopoietic development and function without evidence of toxicity.

--- End quote ---

Very interesting, especially the humanized animal reactions to it so far.   I'm really excited to volunteer the more I learn about Callimune.  I'm more than ready to help move medical science forward.  As with anything new, the first run has the potential for yet another failure.  Having said that,  I'm still feeling more confident 2013 could be a true breakthrough year with cure or "functional" cure news.  I think we are all growing restless with the "cure" news popping up each year that soon fades into the what happened to it category. 

I didn't realize this was hitting both R5-tropic & X4-tropic HIV. (I thought it was a dual approach to R5 only)   Any friends I talk to about CCR5 cures usually remind me about the XCR4 re-exposure threat out there.   I'm really impressed that they are able to move forward with the dual approach. 

JazJon:
Here's an update.   I assumed groups 1, 2 & 3 were happening at the same time but I was mistaken.

-Group 1 (no-chemo) is screening right now, and treatment is then weeks away.
-Group 2 (low-chemo) is screening at the end of 2013, and treatment early  2014
-Group 3 (medium-chemo) is screening mid/end 2014 and treatment 2015

I'm on the list.   Based on the results of Group 1, I'll have to decide if I want to do Group 2 sooner, or wait an extra year for Group 3.  I'm looking forward to seeing how the Group 1 responds, and happy at least a few people are trying out the actual treatment process before I will. (assuming I qualify etc)

It's too early to tell if low vs med chemo pre-conditioning will be all that important.   If Group 1 has outstanding results, I'd drive into Group 2 no questions.  If Group 1 only has ok'ish results, then I might wait the extra year for Group 3.    I'm happy to be in ANY Group to be honest, & just typing up my thoughts.   

I'm glad I formed a good relationship with Quest early on to at least be on the list.
(and looking forward to that call in a few months)  I'm apparently their healthiest patient :)

Here's the other interesting thing.  Calimmune only have 12 slots total SHARED between LA and SF.   Apparently it's almost a first come first serve thing based on screening etc.  That's 4 slots per group, and it's hard to say who will get more LA or SF.   So again having said that, I'd be happy to be in ANY group with such a small number of spots potentially available.

P.S. Group 1 is full obviously, so if you haven't already signed up, it will be a long shot at this point.    Let's hope this actually works and turns into a Phase I/II/III trial by 2016!

POZnLA:

--- Quote from: JazJon on May 01, 2013, 06:22:20 PM ---Here's an update.   I assumed groups 1, 2 & 3 were happening at the same time but I was mistaken.

-Group 1 (no-chemo) is screening right now, and treatment is then weeks away.
-Group 2 (low-chemo) is screening at the end of 2013, and treatment early  2014
-Group 3 (medium-chemo) is screening mid/end 2014 and treatment 2015

--- End quote ---

Thanks for update JazJon, I received similar info here in LA, from UCLA, They said that the 3 groups were consecutive, not concurrent with a review for safety after each group gets into the study, at what point that review occurs I am unsure. The study recruiting opened 4/15/13 and the study has a estimated primary completion date of June 2015, that's according to the listing on clinicaltrials.gov. Based on that and some dates I was given for screening and the apheresis. I was assuming that it was going faster then that. Maybe not.

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