NR - Interim Results in a Patient Subset Indicate That Treatment With
REMUNE(TM) and Antiviral Drugs May Stimulate 'Killer' T Cell Activity
Clinical Trial Data from Phase 2 Spanish Trial Reported at the Fifth
European Conference on Experimental AIDS Research (ECEAR) 2000
CARLSBAD, Calif., Jun 21, 2000 /PRNewswire via COMTEX/ -- The Immune Response
Corporation (Nasdaq: IMNR) announced today preliminary interim clinical results
which indicate REMUNE(TM) (HIV-1 Immunogen) may stimulate cytotoxic T
lymphocytes (CTL) or "killer" T cell activity specifically against HIV, the AIDS
virus, in people infected with HIV concurrently on antiviral drug therapy (ART).
These data represent two-year immunological results from a Phase 2 clinical
trial of REMUNE, an investigational product, currently being tested in Spain
(STIR-2102). These data were presented on June 18 at the Fifth European
Conference on Experimental AIDS Research (ECEAR) 2000 in Madrid, Spain. CTLs are
white blood cells of the immune system (CD8 lymphocytes) capable of directly
killing virus-infected cells.
"These data suggest that treatment with REMUNE may enhance the immune system's
reserves of HIV-specific CTLs. This is very significant because CTL immune
responses are typically lost, or decline to very low levels, in people
chronically infected with HIV despite successful control of viral replication
with antiviral drug therapy," said Professor Eduardo Fernandez-Cruz, M.D., Head
of the Division of Clinical Immunology at University General Hospital "Gregorio
Maranon" in Madrid and Principal Investigator of the Spain trial. "Because CTLs
detect and kill virus-infected cells, boosting the population of CTLs that
specifically react to HIV may enable REMUNE to have a favorable impact on viral
load."
Data on the blood samples taken 24 months into the Phase 2 trial from
pre-selected sites were analyzed in such a way as to ensure that the trial
remains blinded. Immunological tests were performed to measure the effect of
treatment with REMUNE on CTL immune responses as well as CD4 "helper" T cells,
which are the specific targets of HIV infection.
Dr. Fernandez-Cruz reported that in the subset of patients tested for CTL
activity specific to HIV, all the patients tested receiving ART plus REMUNE
showed significant CTL activity specifically against the virus, while all the
patients tested receiving ART plus placebo showed little or no CTL activity in
the same test. In addition, a significant increase in the overall number of
memory CD4 T cells and memory CD8 T cells was observed in REMUNE versus placebo
groups of the subset. (Memory T cells are formed after exposure to a pathogen
and increase the immune system's ability to mount a swift attack when challenged
again with the same pathogen.) The proliferation of CD4 T cells in response to
HIV-1 antigens as well as production of a soluble cytokine, interferon-gamma,
which is a measure of helper T-CD4 cell function, was significantly higher in
the ART plus REMUNE group (27 patients) compared to the ART plus placebo group
(27 patients). The interferon-gamma levels were also strongly correlated with
levels of anti-HIV factors secreted by CD8 T cells (such as the beta-chemokines,
RANTES and MIP-1 beta).
"Helper T cell immune responses and activated CTL precursors appear to increase
in the patients with length of time of vaccination. These data provide evidence
that some constant level of exposure to HIV, as with a therapeutic vaccine, may
be necessary to induce the immune system to generate an immune response against
the virus," said Dr. Fernandez-Cruz. "Of particular note," he continued,
"REMUNE-treated individuals had helper T cell immune responses, which most
likely activated and expanded the CTLs which have the capability to kill
infected cells. We hope that such anti-HIV immune responses will translate into
an enhancement of viral suppression, which is important for long-term management
of HIV-1."
Background
CTLs or CD8 killer T cells are believed to play an important role in combating
HIV infection by at least three different mechanisms, which may not be mutually
exclusive. First, CTLs are capable of directly killing HIV-infected cells by
releasing cytotoxic molecules (e.g., perforin) that lyse, or punch holes, in
those cells causing them to die. Without the host's cellular machinery, HIV
cannot replicate. Second, CTLs also release another set of factors that include
beta chemokines (e.g., RANTES, MIP-1 alpha, MIP-1 beta) that compete with HIV
particles for preferred entry sites on the surface of helper T cells, thereby
thwarting the hallmark viral invasion of the helper T cell population. Finally,
CTLs also release factors called cytokines that suppress the ability of the
virus to replicate within an already infected host cell.
The REMUNE (STIR-2102) study in Spain is a double blind placebo-controlled
trial, which enrolled 243 HIV-infected patients naive to antiviral drugs prior
to time of enrollment. The efficacy of REMUNE administered in combination with
antiviral drugs will be assessed by comparing the time to increases in viral
load or decrease in CD4 helper T cell counts between patient groups that
received ART plus REMUNE or ART plus placebo. The trial is being conducted at 13
clinical centers throughout Spain. |
