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Author Topic: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug  (Read 2847 times)

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Offline contagion

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  • Posts: 72
I came across this old news article posted in July 2012 - don't think it has be posted here.

http://globenewswire.com/news-release/2012/07/24/274260/263132/en/Karolinska-Institutet-and-Immunomedics-Develop-New-Anti-HIV-Drug.html

Strangely can't find the drug in Immunomedics's product pipeline
http://www.immunomedics.com/products.shtml
I have a t-shirt with my t-cells on it.

Offline Cosmicdancer

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Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #1 on: January 27, 2013, 08:39:40 AM »
Can you copy and past the text for the article?  You need to sign in to read it.
Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable
May, 2014 - undetectable, 784 cd4, 48%

Offline Matts

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tivicay/kivexa

Offline contagion

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Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #3 on: January 27, 2013, 02:31:07 PM »
Here you go:
STOCKHOLM, Sweden, and MORRIS PLAINS, N.J., July 24, 2012 (GLOBE NEWSWIRE) -- The Karolinska Institutet, Sweden, together with Immunomedics, Inc. (Nasdaq:IMMU), today announced that their scientists have published an article in the current issue of the journal, PLoS One, describing their collaboration in the design and testing of a new class of drugs that significantly destroyed the AIDS virus, HIV (Human Immunodeficiency Virus), and may potentially eradicate the virus completely.

According to the senior author, Professor Britta Wahren of the Karolinska Institutet, "These new molecules have three distinguishing features. First, each comprises four copies of enfuvirtide (Hoffmann-LaRoche), an approved peptide that prevents the virus from infecting immune cells. Second, the multiple peptides are linked to a humanized antibody without compromising their activity. Third, the incorporation of the peptides to the antibody confers additional benefits, such as enhanced anti-viral potency and improved pharmacokinetics," Professor Wahren explained. "As a result, both infected cells and activated enhanced virus replication have been destroyed in cell culture," she added.

The construction of this new class of anti-HIV agents was enabled by Immunomedics' proprietary Dock-and-Lock (DNL) technology.

Immunomedics' President and Chief Executive Office, Cynthia L. Sullivan, remarked: "We are delighted with this collaboration with two renowned Swedish research groups studying methods to control HIV. The next step is to combine this new molecule with standard HIV therapy in order to potentially eradicate all infected cells." "These studies build on the preclinical work our groups completed a few years ago, where we showed efficacy in controlling HIV-1 infection in mice with an antibody-drug conjugate developed by Immunomedics. The potential future clinical development will be the responsibility of the Karolinska Institutet," she explained further.

The referenced publication is: Chien-Hsing Chang, Jorma Hinkula, Meiyu Loo, Tina Falkeborn, Rongxiu Li, Thomas M. Cardillo, Edmund A. Rossi, David M Goldenberg, Britta Wahren, A Novel Class of anti-HIV agents with Multiple Copies of Enfuvirtide and Prolonged Serum Half-life Enhances Inhibition of Viral Replication and Cellular Transmission in Vitro (http://dx.plos.org/10.1371/journal.pone.0041235).

About HIV and AIDS

After 30 years of the HIV epidemic, the virus is still spreading in all countries of the world. Over 30 million people alive are infected with HIV. Effective anti-viral treatment has radically decreased the viral load and prolonged survival of HIV-infected patients, but this treatment cannot eradicate the virus from the body. After infection, the virus immediately copies itself in normal genes of the patient, and is therefore a life-long passenger in its new host.

About the Karolinska Institutet and Linköping´s University

The Karolinska Institutet is one of the world's leading medical universities. Its mission is to contribute to the improvement of human health through research and education. Located in Stockholm, it has a faculty of 300 professors involved in diverse medical graduate studies. Since 1901, the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine. The Linköping University is a research-based university with excellence in education and a strong tradition of interdisciplinarity and innovation.

About Immunomedics

Immunomedics is a New Jersey-based biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases.  We have developed a number of advanced proprietary technologies that allow us to create humanized antibodies that can be used either alone in unlabeled or "naked" form, or conjugated with radioactive isotopes, chemotherapeutics, cytokines or toxins, in each case to create highly targeted agents.  Using these technologies, we have built a pipeline of therapeutic product candidates that utilize several different mechanisms of action.  We also have a majority ownership in IBC Pharmaceuticals, Inc., which is developing a novel Dock-and-Lock (DNL) methodology with us for making fusion proteins and multifunctional antibodies, and a new method of delivering imaging and therapeutic agents selectively to disease, especially different solid cancers (colorectal, lung, pancreas, etc.), by proprietary, antibody-based, pretargeting methods.  We believe that our portfolio of intellectual property, which includes approximately 202 patents issued in the United States and more than 400 foreign patents, protects our product candidates and technologies.  For additional information on us, please visit our website at http://www.immunomedics.com/ blocked::http://www.immunomedics.com/">www.immunomedics.com.  The information on our website does not, however, form a part of this press release.

This release, in addition to historical information, may contain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995.  Such statements, including statements regarding clinical trials, out-licensing arrangements (including the timing and amount of contingent payments), forecasts of future operating results, potential collaborations, and capital raising activities, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein.  Factors that could cause such differences include, but are not limited to, risks associated with any cash payment that the Company might receive in connection with a sublicense involving a third party and UCB, which is not within the Company's control, new product development (including clinical trials outcome and regulatory requirements/actions), our dependence on our licensing partners for the further development of epratuzumab for autoimmune indications and veltuzumab for non-cancer indications, competitive risks to marketed products and availability of required financing and other sources of funds on acceptable terms, if at all, as well as the risks discussed in the Company's filings with the Securities and Exchange Commission.  The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.
I have a t-shirt with my t-cells on it.

Offline geobee

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Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #4 on: January 28, 2013, 06:06:35 AM »
Well, I waded through the article, 90% of which was over my head (admittedly that's a rather low bar...)

From what I gathered they link an antibody to Fuzeon and, in vitro at least, it seems to be potent at eliminating latently infected cells.   It also seems to hang around in the blood stream for at least 3 days, which would allow daily dosing.  They showed than any antibody -- an HIV specific one or not -- combined with Fuzeon was effective against HIV in latent cells.   They don't know why it's effective with a non-HIV specific antibody.

Many tests remain to be done -- including tests with Fuzeon resistant cells.  And then, of course, animal studies to determine efficacy, toxicity, etc.

(I can't figure out why they didn't try it in vivo with HIV infected mice to see what happens to VL -- seems like that's an obvious and easy thing to do)

So...it seems very clever, and very promising.  It also seems like they have a long way to go before it enters human trials.  On the other hand, they are already using an existing approved drug, hopefully this will speed up the trials process.
« Last Edit: January 28, 2013, 06:08:12 AM by geobee »

Offline Jmarksto

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Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #5 on: January 28, 2013, 09:29:30 AM »
Thanks Geo...
JM
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
02/25/14 CD4   792/37%  VL UD
07/09/14 CD4 1004/39%   VL UD

Offline Mishma

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    • Marquis de Vauban
Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #6 on: January 28, 2013, 02:41:57 PM »
"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.
« Last Edit: January 28, 2013, 02:48:01 PM by Mishma »
2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline Dr.Strangelove

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Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #7 on: January 30, 2013, 11:34:07 AM »
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?

Offline Matts

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Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #8 on: February 05, 2013, 06:29:34 PM »
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.
tivicay/kivexa

Offline Dr.Strangelove

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Re: Karolinska Institutet and Immunomedics Develop New Anti-HIV Drug
« Reply #9 on: February 06, 2013, 08:36:25 PM »
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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