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Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug

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Jmarksto:
Thanks Geo...
JM

Mishma:
"Since most the effector functions of antibodies are mediated by the binding of the heavy chain C regions (part of the Fc region of the antibodies discussed) to Fc receptors on different cells, such as phagocytes (macrophages, neutrophils, microglial, and dendritic cells), NK cells, and mast cells, and to plasma proteins, such as complement proteins."

from Cellular and Molecular Immunology, 7th edition, Abbas, Litchman, Pillai.

Since Ig antibodies have the longest half lifes of all the antibodies it would make sense to use this one. Interfering/modulating with binding to effector cells with HIV specific antibodies ONLY makes this ex tantalizing line of enquiry. The drawback is that humanized antibodies are ex expensive to produce making them impractical in resource poor settings.

From that same paper:

Moreover, depending on the targeting specificity and effector functions of the conjugated antibody, whether binding, neutralizing or not, the resulting DNL constructs could eliminate both infected cells and free virus via several known mechanisms [7]–[9], including complement-mediated lysis, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated virus inhibition (ADCVI), and induction of apoptosis.

Thanks for the post.

Dr.Strangelove:
Just had a quick look at it but I don't really get it either.
So, they linked a fusion inhibitor (which have been around for a while) with an antibody. So far so good.

But how is that going to target latent cells??? The antibodies recognize (HIV) proteins, not viral DNA incorporated into the host genome.

Well, it seems that in all their tests they used SAHA to 'wake up' the latent cells. SAHA alone just woke them up (obviously). But SAHA in combination with their new drug then got rid of the HIV. However, that doesn't really seem like news.
I don't see the advantage of this drug over others when it comes to adressing the latent cells.

Any thoughts?

Matts:
As I read here:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0041235

only the SAHA did the job on the latent cells. So it is nothing exciting, there are many threads about Vorinostat here. I don't know if it was ever tried in HIV patients, this could be interesting in the future.

Dr.Strangelove:
That's what I thought, thanks...

I believe to remember to have read that there were some studies going on with Vorinostat on HIV patients but can't remember the details.

I'm pretty sure that's a topic that will be addressed in several talks at the upcoming CROI 2013. I'm actually starting to get quite excited about the conference.

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