AIDS at 30: Boosting dendritic cells may be key to new therapy

Posted on 30 Jun 2011 at 6:20pm
Dr. Louis Sloan

In revolutionary new HIV research, Dr. Louis Sloan tests a vaccination that appears to get patients off medication

DAVID TAFFET | Staff Writer
taffet@dallasvoice.com

A revolutionary new vaccine allowed all 19 participants in a trial to stop taking any HIV medications during the investigation that lasted more than a year, according to a local physician participating in the trial.

A few who participated in the trial are back on medication. The majority are not, said Dr. Louis Sloan of North Texas Infectious Disease Consultants, located on the Baylor campus. Sloan is investigating the new HIV vaccine therapy that is individually designed for each person.

In the new therapy, dendritic cells are harvested from a patient through a blood draw. Those cells are then stimulated, boosted with Interferon and peptides in a lab at Baylor Hospital, and then injected back into the patient.

The theory of the vaccine, Sloan said, was to use these immune system cells to boost the CD8 cells, which would keep the HIV under control.

Sloan said Phase 1 of the trial, which primarily tested the safety of the vaccine, recently ended. Effectiveness was a secondary consideration.

The vaccine proved safe: The only side effect was some soreness at the injection site, Sloan said.

But the vaccine appears to have been effective as well — at least temporarily.

The 19 people who participated in the study were all HIV-positive and on medication, and each had undetectable viral loads when the study started.

The cells were reintroduced to the body with four injections over six months. The study lasted a year.

Bryan King, director of clinical research

During the period of the study, most of the patients were able to stop all HIV medications. Although the patients’ viral loads were no longer undetectable, those levels did remain low.

By the end of the study, their CD8 counts rose dramatically while their CD4 cell counts remained above 350 in most cases.

The protocol called for all of the participants to return to their medications at the end of the trial. A few did, Sloan said, but most have decided not to begin taking medication again.

“We’ve had to beg people to go back on medication,” he said.

Sloan’s director of clinical research, Bryan King, said that they are monitoring those patients closely, making sure they do not fall below a CD4 cell count of 350. That’s the lowest level he likes to see before beginning a patient on medication, he said.
Phase 2 will involve 70 to 100 patients.

Before that phase begins, researchers here and in France are evaluating whether the vaccine was more effective against certain strains of HIV or if certain portions of the vaccine combated the virus better than others.

Re-injecting a patient’s own dendritic cells to battle disease is not new. At Baylor, doctors have been treating melanoma successfully for almost a decade with this same method, putting that cancer into full remission.

Sloan doesn’t know if he will have the same success against HIV.

“I’m not sure we’ll ever have a cure with dendritic cells,” he said.

But, he said, he expects the treatment to lead to HIV becoming a long-term, non-progressive disease.

“It’s a reasonable alternative to being on medication,” Sloan said.

Sloan expects Phase 2 of the trial to be ready in 2012 but until then, he said, researchers will evaluate and tweak the vaccine.

Results of the study have not been published yet, but Sloan expects to publish them later this year.

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DEFINITIONS

Dendritic cells are cells in the immune system that process antigen material and present it on the surface to other immune system cells. They act as messengers between the innate and adaptive immunity. Dendritic cells are present in tissues in contact with the external environment, such as the skin and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response.

Antigens are any substance that causes your immune system to produce antibodies against it. An antigen may be a foreign substance from the environment such as chemicals, bacteria, viruses or pollen. An antigen may also be formed within the body, as with bacterial toxins or tissue cells.

Pathogens are agents of disease, and the term most often refers to an infectious organism such as a bacteria, a virus or a fungus. Non-infectious agents of disease, such as a chemical, are also sometimes referred to as pathogens.

The innate immune system provides an immediate, but non-specific response when a pathogen invades the body. If pathogens successfully evade the innate response, the adaptive immune system is activated by the innate response and the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered.

Peptides are a type of amino acid that provide communication throughout the immune system and coordinate and control immune system actions. Peptides are referred to as cytokines in the immune system and through their communication ability they create a chain reaction of activity from cell to cell through “cytokine circuits” to generate and then control the immune response.

T cells are a type of white blood cell that are at the core of adaptive immunity. The T cells are like soldiers who search out and destroy the targeted invaders. There are two primary types of T cells: CD4 cells and CD8 cells.

CD4 cells are “helper” cells that initiate the body’s response to infections. CD4 cells are the host cells that aid HIV in replication. HIV attaches to the CD4 cells, allowing the virus to enter and infect the CD4 cells, damaging them in the process. The fewer functioning CD4 cells there are, the weaker the immune system and therefore the more vulnerable a person is to infections and illnesses.

CD8 cells are also called killer cells. They are instrumental in fighting cancer and viruses. CD8 cells also produce antiviral substances, or antibodies, that help fight off the foreign invader.

B cells are a type of white blood cell — specifically, a type of lymphocyte — many of which mature into what are called plasma cells which produce antibodies — proteins — necessary to fight off infections. Other B cells mature into memory B cells. All of the plasma cells descended from a single B cell produce the same antibody which is directed against the antigen that stimulated it to mature. The same principle holds with memory B cells. Thus, all of the plasma cells and memory cells “remember” the stimulus that led to their formation.

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