"HIV cure research: Scientists create two-headed protein to deplete HIV ... "

[tryingtostay]

"HIV cure research: Scientists create two-headed protein to deplete HIV reservoir"


Years away and only tested in laboratories but it's another hopeful project.  I hope something like this can pass the bbb and get rid of the HIV also in the brain.


Link


Scientists at the National Institutes of Health (NIH) have created a protein that awakens resting immune cells infected with HIV and facilitates their destruction in laboratory studies. The protein potentially could contribute to a cure for HIV infection by helping deplete the reservoir of long-lived, latently HIV-infected cells that can start making the virus when a person stops taking anti-HIV drugs. Further studies in animals and people are needed to determine the viability of this approach.

The researchers found that the protein, called VRC07-αCD3, triggered the activation and killing of latently HIV-infected helper T cells when the cells were taken from patients on antiretroviral therapy and then incubated in the lab with the patients' own killer T cells. In addition, the scientists found a monkey-adapted version of the protein to be safe and well-tolerated when given to monkeys infected with a simian form of HIV and receiving antiretroviral therapy. The researchers are now studying the effectiveness of monkey-adapted VRC07-αCD3 in the animals.

The engineered protein has two ends: one activates T cells by binding to a surface molecule called the CD3 receptor, and the other—based on an antibody called VRC07—powerfully binds to more than 90 percent of HIV strains. VRC07-αCD3 facilitates the killing of latently HIV-infected cells in three steps. First, the CD3-binding end attaches to a resting, HIV-infected helper T cell, activating the cell so it starts making HIV and displaying pieces of virus on its surface. Next, the HIV-binding end of the protein latches onto those pieces of virus while the CD3-binding end attaches to a killer T cell, activating it and bringing it close to the helper T cell. Finally, the activated killer T cell destroys the HIV-infected helper T cell.

A team of scientists at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases, part of NIH, created VRC07-αCD3 under the leadership of VRC Director John R. Mascola, M.D.; former VRC Director Gary J. Nabel, M.D., Ph.D.; and Richard A. Koup, M.D., VRC deputy director and chief of its immunology laboratory.

[Almost2late]

From Dr. Joel's Forum..

Question:

Hi Doctor Gallant, I know its too early to ask for comments but I could not stop my self :-) I am sure you have heard about the new protein ( VRC07-αCD3 ) NIH created. What is your opinion?

Answer:



Yes, we’re all hearing about it at the same time from the same press release. In laboratory studies, the protein activates HIV-infected resting CD4 cells, making them susceptible to destruction when they’re incubated with the patients’ own killer T cells. It’s now moving on to animal studies.

Although a protein in a cell culture is a far cry from a treatment we can use, this is still an exciting development. On election day, I hope you’ll all remember that this is research being done by government scientists at the NIH. If you care about HIV research, or any research for that matter, VOTE!  And please don’t vote for people who don’t believe in science, want to shut down the government, or support across-the-board spending cuts. (I think you know which ones I mean!)

[Jeff G]

I like that update Almost2late !

[freewillie99]

And please don’t vote for people who don’t believe in science, want to shut down the government, or support across-the-board spending cuts. (I think you know which ones I mean!)

Ha...love it. The GOP is the Devil (assuming there was such a being).

[MitchMiller]

One of the lead researchers from Nevada was just interviewed on public radio and he seemed very excited about this technology... perhaps overly optimistic because he predicted this technology could potentially cure HIV in 5 or 10 years.  He said there are at least 3 other groups now working with this technology.

I think this is the same technology:  http://www.unlvrebelyell.com/2015/10/22/unlv-bio-professor-and-team-develop-potential-hiv-cure/

[tryingtostay]

One of the lead researchers from Nevada was just interviewed on public radio and he seemed very excited about this technology... perhaps overly optimistic because he predicted this technology could potentially cure HIV in 5 or 10 years.  He said there are at least 3 other groups now working with this technology.

I think this is the same technology:  http://www.unlvrebelyell.com/2015/10/22/unlv-bio-professor-and-team-develop-potential-hiv-cure/

Thanks for the update, too.

I wonder how long a therapy this would be.
Wonder if it will be in a pill or something engineered to inject in the body and then that's it, like one injection?  hmm

[Jmarksto]

here is an article that notes human trials could start within a year.....

http://tinyurl.com/nqn4lf9

Early study results have been promising thus far, and Macrogenics—a biotech company with investigators working alongside researchers from Duke and the University of North Carolina at Chapel Hill—has obtained a contract from the National Institutes of Health to begin human clinical trials in approximately one year.

[freewillie99]

here is an article that notes human trials could start within a year.....

Jmarksto,

I believe this Duke / UNC collaboration is a similar, but competitive, bi-specific antibody to the one discussed above. Great news and let the best antibody win.

[phenethylamine]

Woah, this is actually the first time I hear about a treatment that attacks the Virus directly.

Current treatments are all indirect, they just starve the Virus by blocking an enzyme it uses to replicate. This latches directly onto the virus....making it not just an antivirus but a virus killer.

Thanks for posting

[tryingtostay]

Woah, this is actually the first time I hear about a treatment that attacks the Virus directly.

Current treatments are all indirect, they just starve the Virus by blocking an enzyme it uses to replicate. This latches directly onto the virus....making it not just an antivirus but a virus killer.

Thanks for posting

This one looks very hopeful, I like the way this one works instead of the other methods

[tryingtostay]

Mods if you would like a separate thread for this I apologize.  It seems like the same idea.  Both studies have been mentioned in this thread..


Towards elimination of HIV reservoirs Link


A little more detailed explanation of DART - Dual Affinity Re-Targeting


Article:

Current antiretroviral therapy can keep HIV in check and prevent AIDS in the vast majority of treated patients. However, as it is unable to eliminate viral reservoirs and cure the infection, patients need to stay on the life-long treatment, and deal with the potential side effects of drugs and chronic inflammation due to low-level viral infection. A study published on November 5th in PLOS Pathogens reports that engineered molecules that target both killer T cells and HIV-infected cells that contain viral envelope protein (Env) can induce killing of the HIV-infected cells and further reduce the levels of detectable HIV expression in blood cells taken from HIV-positive patients on antiretroviral therapy.

The proposed "kick and kill" strategy to eliminate HIV combines pharmacologic activation of latent HIV expression to make infected cells visible to the immune system with subsequent immune-mediated killing. Working on the "kill" step, a team of researchers led by Scott Koenig from MacroGenics in Rockville, USA, and Tomas Cihlar from Gilead Sciences in Foster City, USA, designed and evaluated so-called Dual-Affinity Re-Targeting (DART) bispecific molecules. The molecules have two arms: the first binds specifically to the HIV Env protein, and the second one to CD3, a molecule found on cytotoxic (or killer) T cells. In contrast to using a kill-strategy that is based on HIV-specific killer T cells, the DART CD3-binding arm can potentially recruit and activate any kind of killer T cell, thereby mounting a much broader attack on the Env-expressing target cells.

Based on six different anti-Env antibodies, the researchers generated a set of DART molecules and tested them in a mix of resting CD4 T cells isolated from donors and infected with wild-type HIV isolates and unstimulated CD8 T cells from the same individuals. As opposed to dividing cell lines or mitogen-stimulated latency models, the researchers argue that these cells may better approximate the resting state and corresponding low levels of surface Env expressed on reservoir cells from HIV-infected individuals on antiretroviral therapy. They found that DART-mediated co-engagement of HIV-infected CD4 target and CD8 effector cells results in effector cell activation and target cell killing.

In addition, the researchers were able to show that the DART molecules were capable of reducing the level of HIV expression ex vivo in blood cells isolated from HIV-infected participants on suppressive antiretroviral therapy, suggesting that DART-mediated killing of reservoir cells takes place. "Ultimate proof of reservoir reduction would have to be obtained by in vivo testing of DART molecules", the researchers acknowledge, and suggest that their results "provide support to evaluate the bispecific T-cell redirecting molecules in an animal model of HIV latency to determine whether the HIV reservoir can be safely reduced in vivo."

[sphinxcat]

So many good news these days...but we still have to wait years...