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Author Topic: Anti-bodies combined with radiation  (Read 2410 times)

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Offline geobee

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  • Posts: 288
Anti-bodies combined with radiation
« on: December 03, 2013, 01:34:52 AM »
http://m.medicalxpress.com/news/2013-12-hiv.html

"Researchers have used radioimmunotherapy (RIT) to destroy remaining human immunodeficiency virus (HIV)-infected cells in the blood samples of patients treated with antiretroviral therapy, offering the promise of a strategy for curing HIV infection. Results of the study were presented today at the annual meeting of the Radiological Society of North America (RSNA)."

This seems really wild, but really cool.  The anti-body binds to the virus and then radiation kills the virus.  It works in blood, and it also worked in a simulated blood brain barrier.  See the link.

Offline buginme2

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Re: Anti-bodies combined with radiation
« Reply #1 on: December 03, 2013, 07:32:53 PM »
Here is another article about this study.  I can't say I'd be jumping to be first in line for radiation immunotherapy.

http://www.sciencedaily.com/releases/2013/12/131203091601.htm
Don't be fancy, just get dancey

Offline buginme2

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Re: Anti-bodies combined with radiation
« Reply #2 on: December 04, 2013, 05:33:22 PM »
The following article was emailed to me today from medscape. I'll post it below.  It's kinda exciting/interesting...potential?

Excitement Mounting That Radiation Will Eliminate HIV

CHICAGO — Radioimmunotherapy in conjunction with antiretroviral triple therapy can effectively kill HIV-infected cells from patients, a new study has shown.

"The cells are being steadily killed by a dose of radiation," explained Ekaterina Dadachova, PhD, professor of radiology, microbiology, and immunology at the Albert Einstein College of Medicine in the Bronx, New York.

Dr. Dadachova presented the research to an excited audience here at the Radiological Society of North America 99th Scientific Assembly and Annual Meeting. She began her talk by reminding the audience that the conference started on December 1, World AIDS Day.

The safety of radioimmunotherapy is well established in the field of oncology, where tumor cell burdens are approximately 1000 times greater than those seen in HIV patients being treated with triple therapy. This makes HIV a comparatively light load for radioimmunotherapy, according to those most familiar with the technique.

Current treatment options for HIV include antiretrovirals, which can dramatically increase a patient's lifespan and has transformed HIV from an acute disease. "HIV is now a chronic disease, but people are still dying from it and there is still no cure," Dr. Dadachova said.

Medications suppress viral reproduction, but they do not kill infected cells. Antiretrovirals also have a host of problems, including high cost, toxicity, nonadherence, and drug resistance.

Most important, viremia returns after treatment cessation. This is because both cellular and anatomic reservoirs of HIV in the body maintain the infection.

It has fantastic potential.
At the cellular level, even with antiretrovirals, the patient's body contains long-lived cell populations that are infected with HIV and are capable of surviving for prolonged periods of time. Resting CD4+ T-cells, macrophages, dendritic cells, and hematopoietic cells can all serve as reservoirs for HIV.

Anatomically, HIV also persists in the brain, and this has traditionally been a very difficult area for HIV therapeutics to access.

The world needs a strategy for eradicating HIV, said Dr. Dadachova. She then proceeded to describe her team's strategy using radioimmunotherapy.

The approach is effective against HIV-infected cells because it binds to a specific antigen and kills the cells. To be successful as a therapy, it requires an antigen target that in no way resembles a human antigen. If such an antigen can be found, then "1 or 2 hits per cell is enough to destroy the cell," explained Dr. Dadachova.

Her team used the HIV antigen gp41 to generate the 2556 antibody that binds specifically to HIV-infected cells.


Radiolabeled human antibody binds to the viral gp41 protein expressed on the surface of the HIV-infected lymphocyte and the cell is killed with alpha radiation.
The researchers previously used gp41 radioimmunotherapy in mice with severe combined immunodeficiency that were injected with infected human cells (PLoS One. 2012;7:e31866). "We are basically able to eliminate the HIV-infected cells in those mice," Dr. Dadachova said enthusiastically. More important, they were able to eliminate HIV-infected cells in the brains of the mice.

Although the team's success with mice was exciting, she noted that they still did not know whether radioimmunotherapy would work in patients being treated with antiretroviral therapy. No one could say what the interaction between radioimmunotherapy, HIV, and antiretrovirals would look like. Would the suppressed viral replication also suppress the expression of gp41 below the level needed for radioimmunotherapy?

"That's where the Bill and Melinda Gates Foundation came in," she said. "They funded our study."

This year, Dr. Dadachova and her team performed an ex vivo study on clinical samples. They found that radioimmunotherapy killed the infected patient's lymphocytes over a full range of doses.

They also used an in vitro model to demonstrate that the radiolabeled antibody crosses the blood–brain barrier without disturbing the tight junctions of the cells.

"It has fantastic potential," said Gary Whitman, MD, professor of radiology at the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Dadachova will next be partnering with physicians in South Africa to enroll patients there in the first radioimmunotherapy clinical trial. She said she expects the first results by the end of 2014. She also reported that she is applying to the National Institutes of Health for funding to continue the research in the United States.

The treatment regimen will likely consist of a single injection of radioimmunotherapy, she explained. Because bismuth-213 is a very short-lived isotope, all radioactivity will be gone from the patient in 4 hours. Follow-up testing will reveal whether the patient rebounds and requires another treatment.

Many in the room said the precedence of radioimmunotherapy in the treatment of cancer fuels their hope that people will truly have something to celebrate next World AIDS Day.

Dr. Dadachova and Dr. Whitman have disclosed no relevant financial relationships.

Radiological Society of North America (RSNA) 99th Scientific Assembly and Annual Meeting: Abstract SSK12. Presented December 3, 2013.
Don't be fancy, just get dancey

Offline Tadeys

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Offline Jmarksto

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  • Posts: 529
Re: Anti-bodies combined with radiation
« Reply #4 on: December 04, 2013, 05:52:46 PM »
Bug; Thanks for posting the Medscape article - that was the most detailed article that I have seen on the topic. 

There are a few things that strike be about this; First, it seems to have come out of left field -- there must be all kinds of research going on that we (or at least I) have no idea about. Second, the fact that this treatment is already being used for cancer means the timeline to clinical application will be much shorter than other research -- and as noted in the article to have clinical trial results by the end of 2014 is very exciting.

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
11/03/14 CD4   711/34%   VL UD

Offline xrel0aded

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Re: Anti-bodies combined with radiation
« Reply #5 on: December 04, 2013, 06:03:21 PM »
that is quite exciting indeed- thanks for sharing  8)


Offline Tadeys

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  • Posts: 162
Re: Anti-bodies combined with radiation
« Reply #7 on: December 04, 2013, 10:47:49 PM »
"The antibodies they used bind to a molecule known as GP41, which is found only on the outside of cells carrying the virus"

Do CD4s in latency exhibit GP41? Anybody know?

Offline geobee

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Re: Anti-bodies combined with radiation
« Reply #8 on: December 04, 2013, 11:02:09 PM »
Thanks bug and jarringly for the posts.

From the 2006 article, it looks like it clears *almost* all the cells in the mice.  I wonder -- is that enough?  Do you have to blast every one of the suckers? Or can one's immune system take care of the few that might remain? 

I love the thought of nuking my HIV.  Bring it on!  I can see this therapy working in conjunction with the other AB therapies.  Use the nuke to kill most of the HIV, get an injection of broadly-neutralizing antibodies to mop of the rest.

And thanks, of course, to Dr. Dadachova!  You're a star!

George

Ah -- finally figured out how to get my mug shot posted!


« Last Edit: December 04, 2013, 11:05:11 PM by geobee »

Offline JazJon

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  • Posts: 94
Re: Anti-bodies combined with radiation
« Reply #9 on: December 05, 2013, 04:07:33 AM »
Very interesting.   I learned of the news on Reddit a minute ago.

http://www.reddit.com/r/hivaids/comments/1s2uv0/cure_for_hiv_this_seems_too_good_to_be_true/

Someone said "it doesn't do anything about the latent reservoir"

Let's hope this isn't' true, and it goes somewhere.
« Last Edit: December 05, 2013, 04:16:25 AM by JazJon »

Offline Jmarksto

  • Member
  • Posts: 529
Re: Anti-bodies combined with radiation
« Reply #10 on: December 05, 2013, 03:03:42 PM »
"The antibodies they used bind to a molecule known as GP41, which is found only on the outside of cells carrying the virus"

Do CD4s in latency exhibit GP41? Anybody know?

Someone said "it doesn't do anything about the latent reservoir"
Let's hope this isn't' true, and it goes somewhere.

It seems the $64k question is whether latent cells exhibit GP41.  If they don't perhaps this treatment could be used as the "kill" component of a Kick-and-Kill combined treatment.

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
11/03/14 CD4   711/34%   VL UD

 


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