Radioimmunotherapy treatment for HIV infection

[datdude]

Radioimmunotherapy: Promising treatment for HIV infection and viral cancers
Novel therapy presented in featured lecture at AAAS Annual Meeting
 
     
   
 IMAGE: Radiolabeled antibodies kill HIV infected human cells through binding to viral antigens on these cells.


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February 14, 2009 — (BRONX, NY) — Scientists at Albert Einstein College of Medicine of Yeshiva University have piggybacked antibodies onto radioactive payloads to deliver doses of radiation that selectively target and destroy microbial and HIV-infected cells. The experimental treatment — called radioimmunotherapy, or RIT — holds promise for treating various infectious diseases, including HIV and cancers caused by viruses. The research was presented today at the annual meeting of the American Association for the Advancement of Science (AAAS), the world's largest general scientific society and the publishers of the journal Science.

The talk, part of the AAAS Topical Lecture Series, was delivered by Ekaterina Dadachova, Ph.D., a leading RIT researcher at Einstein. Dr. Dadachova is the Olnick Faculty Scholar in Cancer Research, as well as an associate professor of nuclear medicine and of microbiology & immunology at the College of Medicine.

RIT, which is currently used in cancer treatment, capitalizes on the fact that each type of antibody is programmed to seek out just one type of antigen in the body. Thus, by attaching radioactive material to a particular antibody, radiation can be targeted at specific cells that express the corresponding antigen, minimizing collateral damage to other tissues. This level of specificity is not possible with existing forms of radiation therapy.

RIT was originally developed as a therapy for cancer treatment and has been the most successful so far in treatment of non-Hodgkin lymphoma, a cancer that originates in cells of the immune system. Over the last few years, in collaboration with Dr. Arturo Casadevall, Chair and Forchheimer Professor of Microbiology & Immunology at Einstein, Dr. Dadachova has adapted the technique for fighting fungal, bacterial, and viral infections. Drs. Dadachova and Casadevall performed these studies in conjunction with scientists at Einstein and NYU, and at the European Commission Joint Research Centre; the latter of which supplied some of the important radionuclides for arming the antibodies.

Since viruses are quite different from cancer cells, devising radioimmunotherapy for HIV posed significant challenges. Viruses are tiny bits of DNA or RNA wrapped in a thin protein coat. Simple, tough, and resilient, viruses easily shrug off radiation directed at them and can readily repair any damage that might occur. Complicating matters, HIV can hide in immune cells keeping the virus beyond the reach of antibodies.

"Our approach is not to target the virus particles themselves, but rather lymphocytes that harbor the virus," says Dr. Dadachova. "Fortunately, lymphocytes are among the most radiosensitive cells in the body."

The RIT devised by Einstein researchers consists of an antibody for glycoprotein 41 (gp41) and a radioactive isotope called Bismuth-213, bound together with a special molecule known as a ligand. The gp41 antibody was selected because its corresponding gp41 antigen is reliably expressed on the surface of cells infected with HIV. In addition, unlike other HIV-related glycoproteins, gp41 antigen usually is not shed into the bloodstream, which would lead many of radioactive-labeled antibodies to miss their target. Bismuth-213 was chosen because of several characteristics, including a half-life, or decay rate, of 46 minutes. Such a short half-life rate allows just enough time for the treatment to be administered and for the radioactive antibodies to do their job. After four hours, Bismuth-213 radioactivity falls to negligible levels.

Drs. Dadachova and Casadevall and their colleagues have demonstrated that the treatment can effectively eliminate HIV-infected human cells in both laboratory and animal studies, the latter involving two different models of mice with HIV. The team is now conducting pre-clinical testing of the therapy's efficacy and safety in preparation for a Phase I clinical trial in HIV-infected patients.

RIT also has potential as a therapy for cancers that are preceded by viral infections, such as cervical cancer (certain forms of which are associated with human papilloma virus) and hepatocellular carcinoma (associated with hepatitis B virus). Such cancers account for almost a quarter of all cancers. "Many virus-associated cancer cells continue to express viral antigens," Dr. Dadachova explains. "As these antigens are not found anywhere else in the body, RIT of viral cancers promises exquisite specificity of treatment and very low toxicity to the patient."

http://www.eurekalert.org/pub_releases/2009-02/aeco-rpt021309.php

[HALOO]

This sound interesting

[Inchlingblue]

Drs. Dadachova and Casadevall and their colleagues have demonstrated that the treatment can effectively eliminate HIV-infected human cells in both laboratory and animal studies, the latter involving two different models of mice with HIV. The team is now conducting pre-clinical testing of the therapy's efficacy and safety in preparation for a Phase I clinical trial in HIV-infected patients.
[/quote]

This study sounds very interesting and promising. I wonder if, when they say that the treatment can "effectively eliminate HIV-infected human cells in both laboratory and animal studies," if they mean ALL HIV-infected cells, including the reservoirs where HIV lurks and hides?

[mpositive]

I also found this to be very interesting.  Reading todays articles on the subject, this really does seem like it has potential.  I think the issue will be what kind pf permanent damage will be done to the body and does it out weigh living with the virus.
We shall see, certainly one to watch.
M

[J220]

I also found this to be very interesting.  Reading todays articles on the subject, this really does seem like it has potential.  I think the issue will be what kind pf permanent damage will be done to the body and does it out weigh living with the virus.
We shall see, certainly one to watch.
M

No question, there will always be risks associated with any radioactive treatment, but given the fact that the half life of the isotope is so short, and that the radioactive payload is going directly to the pathogens that the antobodies are targeting I think the risks with RIT for HIV will be minimal.

Overall, I am very optimistic about this possible treatment. In particular because it actually worked in targeting and eliminating hiv infected cells in mice. True, it still has to translate to humans, but since this is not a vaccine that is designed to make the body create antibodies, but rather the antibodies are already provided that will target the infected cells, and thus carry the isotopes there to kill off that particular cell, I think the success with the animal models will be duplicated in humans. High hopes for this one!

[J220]

opps! double post sorry.

[veritas]

Drs. Dadachova and Casadevall and their colleagues have demonstrated that the treatment can effectively eliminate HIV-infected human cells in both laboratory and animal studies, the latter involving two different models of mice with HIV. The team is now conducting pre-clinical testing of the therapy's efficacy and safety in preparation for a Phase I clinical trial in HIV-infected patients.


This study sounds very interesting and promising. I wonder if, when they say that the treatment can "effectively eliminate HIV-infected human cells in both laboratory and animal studies," if they mean ALL HIV-infected cells, including the reservoirs where HIV lurks and hides?

Inchlingblue,

Earlier studies seem to point to eliminating all infected cells (including the reservoirs).

http://www.sciencedaily.com/releases/2006/11/061107082943.htm

J220,

I agree with you with respect to targeted antibodies and "colateral damage".  When a therapy is targeted their is less stress on the untargeted cells . This targeted mechanism is also true of anti-ps  therapy which has shown remarkable safety data in human clinical trials for both cancer and Hepc.
Radioimmunotherapy  is another one to watch.

veritas

[sensual1973]

from this article i understand that the RIT targets lymphocytes that harbor the virus,but what will happen to the virus floating in the blood stream damaging the CD4 cells

peace

[veritas]

from this article i understand that the RIT targets lymphocytes that harbor the virus,but what will happen to the virus floating in the blood stream damaging the CD4 cells


peace

Sensual1973,

The targeted antibodies will also go after freeflowing virus infected cells. From the article linked:


"The study included some test-tube experiments on HIV infected human white blood cells as well as experiments on HIV infected mice that were injected with the radioactive antibodies. The researchers found that HIV infected white blood cells were successfully killed by radioactive antibodies that had been developed against specific proteins in the HIV particle that are routinely displayed at the surface of infected cells. "

veritas

[sensual1973]

thanx veritas

i hope human trials strat as soon as possible now and not wait for another few years.

peace