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1980 smallpox had been eradicated
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May 23, 2010)
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20 May 2010
Researchers have identified how a normal response to infection, one that usually
serves to limit the amount of inflammation, actually contributes to disease
progression and viral persistence in HIV-infected patients.
The findings, published in the May 19 issue of the journal Science Translational
Medicine, offer important opportunities for further research, both for treatment
of long-term persistence of HIV in those who are infected and for prevention of
infection in those who are not, according to the study team.
The study, led by UCSF researchers, focused on the body's production of an
enzyme called indoleamine 2,3-dioxygenase 1 (IDO1). To prevent the harm
associated with chronic inflammation, the body typically turns on IDO1, which
then serves to suppress inflammation and immune responses. In the setting of HIV
infection, the authors found that IDO1 can instead alter the balance between two
types of T-cells that have opposing functions.
One type of immune cell, called Th17, releases interleukin-17, a cytokine that
has a central role in maintaining the integrity of the mucosal barrier in the
gut. The other type, named Treg, prevents inflammation in a non-specific manner
and can also turn off immune responses against viruses such as HIV.
The authors found that induction of IDO1 by HIV results in loss of Th17 cells
and a relative increase in Tregs. This change in the balance of Th17 cells and
Tregs allows bacteria to cross the mucosal barrier of the gut, initiating new
inflammatory reactions in the process. At the same time, the increased number of
Tregs may prevent the immune system from attacking HIV in areas of the body
where strong HIV-specific immune responses are most needed. The altered Th17/Treg
balance, in sum, leads to an endless cycle of inflammation induced by the
invading microbes, more induction of IDO1, and continued loss of Th17 cells.
"In most instances, reducing inflammation following immune system
activation to fight infection is beneficial. But, in HIV disease, this can
establish a reinforcing cycle that is strongly linked to disease progression and
that may help HIV to persist in patients, said study lead co-author, Jeff Mold,
PhD, from the UCSF Division of Experimental Medicine. "Mucosal defenses are
breached, microbes cross over, and inflammation results. This leads to
increasing IDO1 activity, continued changes in the balance of Th17 and Treg
cells, further weakening of the mucosal defenses, and even more
inflammation."
The findings represent the next step in a series of research studies reported
previously by the same group of investigators, showing that SIV infection of
monkeys leading to AIDS is associated with a similar change in Th17 and Treg
balances. The change in T cell balance was not observed in another primate,
African green monkeys, where infection with SIV is harmless and does not cause
disease.
In the current study, the investigators looked at IDO1 activity in HIV-infected
human subjects at various stages of disease and in healthy non-infected
subjects.
"We confirmed that IDO1 activity is associated with HIV disease
progression. But we went further and also looked at the Th17 and Treg balance,
and found that the change in the ratio leading to decreasing Th17 cells is also
associated with HIV disease progression," said study lead co-author, David
Favre, PhD, formerly at UCSF, now with the National Immune Monitoring
Laboratory, Montreal.
With pharmacological inhibitors of IDO1 in development and currently in clinical
trials for cancer immunotherapy, the finding may lead to new therapeutic
approaches for assisting in the control of HIV disease, noted the study team.
"Most of an infected person's own immune responses that are known to affect
HIV disease outcomes cannot be manipulated or altered clinically and, hence,
have not really had much of an impact for patients. This work, however, is very
different, as it has uncovered several possible pathways that might be addressed
clinically with developing or available therapeutics," said study
co-author, Steven Deeks, MD, professor of medicine at the UCSF Division of
HIV/AIDS at
IDO1 may play a role in the ability of HIV to persist in HIV-infected patients
for their lifetimes, notwithstanding effective treatment with antiretroviral
therapies.
"Steve Deeks and I are continuing to examine the role of IDO1 through a
study recently announced by amfAR, the Foundation for AIDS Research, into
whether the disruption of IDO1 will reduce the level of immune activation, which
could then lead to a decrease in viral persistence," said senior study
author Joseph M. McCune, MD, PhD, chief of the UCSF Division of Experimental
Medicine.
In addition to Favre, Mold, Deeks, and McCune, other study co-authors include
Peter Hunt, Bittoo Kanwar, Lillian Seu, Jason Barbour, Margaret Lowe, Anura
Jayawardene, Francesca Aweeka, Yong Huang, Jeffrey Martin, and Frederick Hecht
from UCSF; Daniel Douek and Jason Brenchley from the National Institute of
Allergy and Infectious Diseases, NIH, and P'ng Loke from NYU.
The research was funded by grants from the Elizabeth Glaser Pediatric AIDS
Foundation, the National Institute of Allergy and Infectious Diseases, the
National Institutes for Health, the Harvey V. Berneking Living Trust, the
Source:
20 May 2010
After two decades of setbacks in developing vaginal microbicides that women
could use to protect against HIV, researchers have turned their focus to vaginal
gels and rings infused with antiretroviral drugs, the AP/Atlanta
Journal-Constitution reports. This weekend, microbicide experts will meet in
According to the
AP/Journal-Constitution, women-controlled HIV prevention methods are considered
a crucial piece of curbing the spread of the disease, especially in developing
countries, where the epidemic is most severe and women's partners might be less
likely to use condoms.
After oral antiretroviral drugs proved successful in extending the lives of
people with HIV and reducing the risk for mother-to-child transmission,
scientists began exploring whether preventive daily treatment with
antiretrovirals could prevent HIV infection, according to the
AP/Journal-Constitution. Several studies are underway to test the strategy,
known as pre-exposure prophylaxis. However, the preventive pills also have
drawbacks -- such as systemic side effects, the risk of drug immunity and
problems from missed doses -- highlighting the need for topical protection.
Results of the first study testing an antiretroviral-infused vaginal gel are
expected in July. The trial followed 900 HIV-negative women in
Researchers hope that tenofovir vaginal gels could help stop the virus from
reproducing in the vaginal wall before it spreads throughout the body. In
addition, because the tenofovir gel does not spread significantly beyond the
vagina, side effects might be less severe than when the drug is taken in pill
form, experts say.
Meanwhile, other researchers are recruiting 5,000 HIV-negative women in
BBC 17 May 2010
|
By
1980 smallpox had been eradicated |
The worldwide eradication
of smallpox may, inadvertently, have helped spread HIV infection, scientists
believe.
Experts say the vaccine
used to wipe out smallpox offered some protection against the Aids virus and,
now it is no longer used, HIV has flourished.
The
But they say in the
journal BMC Immunology it is too early to recommend smallpox vaccine for
fighting HIV.
Kill no cure
Lead researcher Dr Raymond
Weinstein, from
"However, all of
these have been either disproved or do not sufficiently explain the behaviour of
the HIV pandemic."
|
|
|
Dr Weinstein and his
colleagues believe immunisation against smallpox may go some way to explain the
recent rises in HIV prevalence.
Smallpox immunisation was
gradually withdrawn from the 1950s to the 1970s, following the worldwide
eradication of the disease, and HIV has been spreading exponentially since then,
they say.
Now, only scientists and
medical professionals working with smallpox are vaccinated.
To test if the events may
be linked, the researchers looked at the white blood cells taken from people
recently immunised against smallpox and tested how they responded to HIV.
They found significantly
lower replication rates of HIV in blood cells from vaccinated individuals,
compared with those from unvaccinated controls.
The smallpox vaccine
appeared to cut HIV replication five-fold.
Immune boost
The researchers believe
vaccination may offer some protection against HIV by producing long-term
alterations in the immune system, possibly including the expression of a
receptor called CCR5 on the surface of white blood cells, which is exploited by
the smallpox virus and HIV.
Jason Warriner, clinical
director for the Terrence Higgins Trust, said: "It's impossible to say
whether the withdrawal of the smallpox vaccine contributed to the initial
explosion of HIV cases worldwide, but it is a plausible explanation.
"This is an
interesting piece of research, and not just as a history lesson. Anything that
gives us greater understanding of how the virus replicates is another step on
the road towards a vaccine and, one day, a cure.
"Further studies into
the role receptor cells play are needed, and even then any discoveries are
likely to be just one part of the solution.
"Until we find a way
to eradicate the virus from the body, the focus should remain on stopping it
being passed on in the first place."
|
By Jane Dreaper |
|
The
virus can spread from mother to baby |
A
campaign is being launched to try to enlist public support to ensure no more
children are born with HIV by 2015.
It
is the work of the Global Fund, which uses donations from governments to fight
HIV, TB and malaria.
The
Born HIV Free campaign comes at a critical time, with the fund seeking donations
of up to $20bn over the next three years.
It
recognises this will be a battle, as governments deal with the aftermath of the
Greek financial crisis.
HIV
can be passed from mother to child during pregnancy, labour or breast-feeding.
This
type of transmission has been almost wiped out in countries such as the
Other
measures - such as giving birth by caesarian section - help stop HIV being
transmitted to the baby.
But
in developing countries, 430,000 children are born with HIV every year.
International
effort
The
Global Fund already channels more than half of international resources used to
prevent mothers passing on HIV.
It
believes that the goal of ending this type of HIV transmission by 2015 is
achievable - if governments feel they can pledge money with the support of their
electorates.
Its
executive director, Professor Michel Kazatchkine, said: "We can win this
battle against Aids if we get the funding we require.
"This
campaign is intended to encourage people to sign up in support of the Global
Fund, and to show their leaders that there is strong public support to continue
and increase funding for its mission."
Endorsement
The
campaign has been overseen by the French first lady, Carla Bruni-Sarkozy, who is
an ambassador for the Global Fund.
Her
voice urges people to lend their support in a series of films, with music by Amy
Winehouse and U2, which are being promoted on the internet.
The
logo has adapted the visual imagery of the red ribbon - long associated with
AIDS awareness - to symbolise a mother and child.
The
The
next round of donations will be confirmed at a crucial meeting in October,
chaired by the UN secretary-general Ban Ki-moon.
Insiders
at the Global Fund are waiting to hear how the new coalition government in the
They
say they have previously had "promising noises" from the Conservatives
and Liberal Democrats on global health issues.
The
editor of the Lancet medical journal, Dr Richard Horton, said: "An early
indication that our government will support the Global Fund is really important.
"It's
something that has worked - because the money has been spent on drug treatment
and bed nets.
"Another
pressing issue is taking a serious look at the Department for International
Development.
"There
is genuine concern that a lot of money has been spent on development aid -
without always getting a clear return.
"There
needs to be accountability at this time of financial stringency."
Long history of SIV suggests HIV won't quickly become benign.
Published online 21 May
2010 | Nature | doi:10.1038/news.2010.259
News
Elie Dolgin
New strains of SIV were
found - and dated - in the drill (pictured), a close relative of the
baboon.Cyril Ruoso/Minden Pictures/FLPA
The HIV-like virus that
infects monkeys is at least 100,000 if not millions of years old, scientists
reported this week at a meeting of the New York Academy of Sciences. The vast
age of the monkey virus, which does not cause illness in most of its hosts,
suggests that it may take a long time for HIV to become equally benign in
humans.
"Don't expect human
evolution to unfold in a timeframe that will do anything good for us,"
Michael Worobey, an evolutionary biologist at the
Most researchers agree
that the pandemic strain of HIV that currently infects more than 33 million
people worldwide started in central
These projections,
however, assume that SIV DNA sequences mutate at the same rate as HIV's modern
pace of evolution, which many say is much faster than historic rates of change.
So some researchers have sought other lines of evidence. A related virus found
embedded within the genome of lemurs from
Geological clock
To pin down the age of SIV,
Worobey teamed up with Preston Marx, a virologist at the
Worobey compared DNA
sequences taken from SIV strains infecting drills from both
"It's compelling and
orthogonal evidence that SIV is a lot older than we previously thought,"
says Sarah Schlesinger, a cellular immunologist at
Using the biogeographical
data from
Regardless of the exact
age, Beatrice Hahn, an HIV researcher at the
References
Sharp, P. M. et al.
Biochem. Soc. Trans. 28, 275-282 (2000).
Wertheim, J. O. &
Worobey, M. PLoS Comput. Biol. 5, e1000377 (2009).
Gifford, R. J. et al.
Proc. Natl. Acad. Sci. USA 105, 20362-20367 (2008).
May 21, 2010
Scientists writing in an
eminent American medical journal have expressed hope of dramatic changes in the
fight against HIV and TB.
According to authors of a
special new issue of the journal Clinical Infectious Diseases, breakthroughs on
the horizon include novel TB drugs in the pipeline that offer the hope of a
safer, faster cure for both standard TB and drug-resistant TB; TB diagnostic
tests that shrink the time it takes to diagnose drug-resistant TB from six weeks
to 90 minutes; and bold HIV prevention approaches that include using
antiretroviral agents as prophylactics to prevent against HIV infection, a
method known as pre-exposure prophylaxis (PrEP).
At a
The briefing featured
Anthony S Fauci, director of NIH's National Institute of Allergy and Infectious
Diseases, and other leading physician-scientists from across the
"Bold new policy,
research, and programmatic approaches are needed to empower the scientific
community to take on these twin diseases," Wafaa El-Sadr, director of the
International Center for AIDS Care and Treatment Programs and professor of
medicine and epidemiology at Columbia University's Mailman School of Public
Health, said.
"These global health
challenges are surmountable. With the right combination of financial resources,
scientific innovation, and political will, the
May 18, 2010
Researchers at
The finding could yield new strategies for prevention or treatment.
The discovery centres around the anti-HIV function of a tiny protein called
prothymosin-alpha.
Previous studies have shown that the protein can block HIV viral replication
once HIV invades a cell, but until now, no one has understood exactly how that
happened.
"But now we have a much clearer understanding of how this protein
works," said Dr. Mary Klotman, senior author of the paper.
The discovery of the antiviral activity of this protein is another piece of the
long-standing quest to define the natural substances made by specific immune
cells, in this case CD8+ T cells, that have potent anti-HIV activity.
The researchers conducted a series of laboratory tests and studies in mice and
in human cells, and discovered that prothymosin-alpha binds to an important cell
receptor called TLR4, and stimulates these cells to produce interferon.
Interferons are part of the body's innate immune system and are powerful,
naturally occurring proteins that can kill many types of pathogens, including
bacteria, cancer cells and viruses, like HCV and HIV.
"We found this fascinating. Usually, it takes an invading virus to trigger
interferon production. But here we have a case where the body's own defence
system "a host protein is inducing it," said Klotman.
"This is a perfect example of two arms of the immune system working
together. A protein produced by CD8+ cells of the adaptive immune system is
exerting potent viral-suppressive activity through a mechanism thought to be
reserved for cells of the innate immune system," said a co-author of the
study.
The researchers performed their experiments in macrophages, special immune cells
that are one of the first lines of defence against viruses and infectious
microbes, and also among the key targets HIV invades.
"Macrophages are also important because we think they also function as a
safe haven for HIV; protective spaces where HIV can hide and bide its time. It's
good to know we've identified a pathway that we might be able to exploit to
sabotage this function," said Klotman.
The scientists said that figuring out how prothymosin-alpha stimulates
production of interferon could reveal novel pathways for protection and
treatment of viral infections.
"But much more work needs to be done. The structure of the protein invites
interaction with other proteins that could potentially affect its current
function,” they said.
The study has been published in the Proceedings of the National Academy of
Sciences.
23 May 2010
Critical Outcome Technologies Inc. (COTI) (TSX VENTURE:COT) today announced
positive results from the first phase of its HIV integrase inhibitor discovery
program. These results provide novel intellectual property to the Company and
further validation of the CHEMSAS® drug discovery technology.
The significance of these results is that the majority of currently marketed and
developmental stage HIV Integrase inhibitors have a very similar way of
interacting with and inhibiting the enzyme through a diketo acid type moiety.
COTI has used its proprietary technology, CHEMSAS®, to discover several novel
small molecule scaffolds that have an entirely new binding mode and interaction
with the active site of the viral enzyme.
COTI has completed the synthesis and initial confirmatory in vitro testing of
the first three novel scaffolds from this program. All three scaffolds
demonstrated good inhibitory activity in a biochemical HIV integrase assay at
nanomolar concentrations. On the basis of these results, COTI has filed
composition of matter patents and intends to proceed with the next phase of this
project that consists of optimizing a small series of potential lead candidates
based on these scaffolds.
"These encouraging results provide further validation of our CHEMSAS®
technology and its ability to rapidly identify innovative small molecules for
difficult drug targets. The discovery of new HIV integrase inhibiting scaffolds
having an entirely novel mode of interacting with the enzyme has been
challenging for HIV researchers, which makes these early results quite
gratifying," said Dr Wayne Danter, COTI's President and CSO.
As previously announced, these novel scaffolds are part of a co-development
program with a major pharmaceutical partner. The co-development partner is now
conducting and funding agreed upon in vitro experiments in their evaluation of
the compounds. Once these experiments have been completed and the results have
been received by COTI, the co-development partner will have an exclusive time
period to negotiate a licensing agreement with COTI for the compounds.
May 22, 2010
Human cells defend
themselves against immune attack by displaying proteins on their surface that
mark them as "self".
When the immune system detects these proteins, it holds back. One way HIV evades
immune attack is by hijacking one of these proteins - CD59 - and using it to
disguise itself and the cells it infects as healthy, human cells.
This cloak doesn't kick in directly following HIV infection. First, antigens on
HIV's surface prompt the immune system to pump out vast quantities of anti-HIV
antibodies, which bind to the antigen and even trigger the destruction of some
HIV.
But once the infection is established, the CD59 cloak prevents further immune
attack on the viral particles and infected cells, which also display the
antigen.
"HIV patients have a very strong antibody response, but unfortunately it
doesn't work," New Scientist quoted Qigui Yu of the Indiana University
School of Medicine in
To kick-start this immune attack, the researchers wanted to find a way to remove
this cloak. They knew that a bacterium found in the human throat secretes a
toxin called intermedilysin that binds to CD59. By isolating the toxin's binding
site they made a small molecule called rILYd4.
When they added this molecule to blood from people with HIV, it enabled the
antibodies already in the blood to destroy viral particles. Red blood cells and
uninfected immune cells were unscathed, probably because there were no
antibodies specific to these cells present.
Yu has preliminary results suggesting rILYd4 fights infected cells too.
The study has been published in The Journal of Immunology.
May 20, 2010
Ali El Kateeb of the
Electrical and Computer Engineering Department, at the
The currently available kits require a drop of blood placed in a well containing
reactant test chemicals. A positive test produces a colored band perpendicular
to a "control" bar that appears only if the test procedure was carried
out correctly.
El Kateeb points out that even such an apparently simple test must be carried
out by a trained technician and in a clinic or laboratory.
Unfortunately, errors in reading the test pattern can occur and are particularly
common in parts of the world where there is a dearth of qualified technicians.
The result is that false positives that have a negative psychological effect on
patients are common while false negatives mean patients thinking they are free
of the virus will continue to infect others unwittingly.
Previously, El Kateeb had developed a static imaging device - akin to a simple
digital camera, that could be used to identify valid and positive test results
using a built-in computer chip modified to run a dedicated pattern recognition
program.
The static approach was not entirely successful because it relies on precise
manufacture of the test kit as well as accurate placement of the "eye"
of the imaging device above the test kit.
Now, El Kateeb has developed a "dynamic" version of the device that
overcomes this significant drawback.
In the dynamic approach, the built-in software embedded on a Reconfigurable
System-On-Chip, first determines the relative position of the detector's 384 W
288 pixel eye relative to the test kit well, illuminated by four LEDs, using a
rapid analysis of pixel density in the captured image. The software
El Kateeb says this dynamic detection technique is 100percent accurate in
laboratory testing. The device is inexpensive, portable and self-contained and
so could be made available to small clinics and pharmacies at low cost.
Moreover, it requires no technician intervention, which will make it useful for
rural areas in the developing world.
The device is described in the International Journal of Biomedical Engineering
and Technology.
May 17, 2010
A new study conducted by
researchers at
"Among HIV-infected persons with suspected TB, falsely diagnosing persons
with TB by rapid testing was associated with increased mortality when compared
with the group of patients who received the correct diagnosis," said study
lead author Robert Blount, clinical fellow in pulmonary and critical care
medicine at UCSF's School of Medicine.
The diagnosis of TB in HIV patients is particularly important, because of their
increased susceptibility to the disease and the time that the standard sputum
culture test takes to reveal results.
In this study, Dr. Blount and his colleagues evaluated the outcomes of 600
HIV-infected patients who were treated at
"Studies tend to emphasize the negative impact of missing the diagnosis of
TB. Our study shows that falsely diagnosing patients with TB who do not actually
have TB is also associated with negative outcomes," Dr. Blount noted.
Because physicians believe tuberculosis is the culprit, any search for the real
underlying disease is delayed, as is proper treatment, he said.
"These results remind us as clinicians that diagnostic tests are not 100
percent accurate, and that falsely diagnosing patients with a disease who do not
actually have that disease can lead to negative outcomes," he said.
"We must continue to re-evaluate a patient's clinical progress. If he or
she is not responding as predicted to treatment for a diagnosed disease, we must
entertain alternative diagnoses," he added.
Dr. Blount also noted the results indicate a need for further refinement of
rapid diagnostic tests for tuberculosis.
The results of the study will be presented at the ATS 2010 International
Conference in
19 May 2010
An inexpensive new test for the detection of Hepatitis B virus has been given
regulatory approval for use in the European Union. The test, developed with
support from the Wellcome Trust, delivers accurate results while-you-wait,
enabling doctors to take immediate action on health decisions.
Hepatitis B virus (HBV) is highly infectious - one hundred times more infectious
than HIV - and is endemic in many parts of the world. In the
The virus is spread through contact with infected blood or other body fluids
including sexual contact. Although the infection rarely kills, it can cause
serious health problems and places a tremendous strain on healthcare resources.
The new Hepatitis B Rapid Test, developed with a Strategic Translation Award
from the Wellcome Trust, uses a dipstick technology to deliver an accurate
diagnosis on-site within half an hour and can be used with minimal training.
Current methods of diagnosis require sending patient samples away to
laboratories for analysis by skilled technicians using expensive machinery,
taking days to weeks to obtain the results.
Professor Baruch S. Blumberg, who was awarded the Nobel Prize for Medicine for
the discovery of the Hepatitis B Virus and the invention of the HBV vaccine
said: "Approval of the new Hepatitis B Rapid Test is positive news for the
estimated 400 million HBV carriers worldwide. Studies have shown that anti-viral
treatment can significantly decrease the risk of death from diseases linked to
HBV infection, but most of the HBV carriers and patients in the world remain
unidentified."
"Being able to identify carriers, initiate immediate treatment of
appropriate candidates, and vaccinate family members and close contacts, has the
potential to greatly accelerate the program to control HBV infection and
spread."
"HBV infection and the diseases related to it are solvable problems. The
Hepatitis B Rapid Test developed by Diagnostics for the Real World can make a
significant contribution to the solution."
Dr Helen Lee from Diagnostics for the Real World, who led the development of the
test said: "Our test is simple, quick, inexpensive and can survive very hot
conditions for many months - all vital factors when you are working in poorer
parts of the world".
The new test is expected to make a vital impact in helping to curb the spread of
disease. The fast turnaround means that doctors will be able to screen pregnant
mothers and take steps to prevent them from passing the virus to their unborn
baby. And the ability to screen donors before they give blood will help to cut
transmission through infected transfusions.
Ted Bianco, Director of Technology Transfer at the Wellcome Trust said "We
are extremely pleased that the product is able to meet the exacting standards
required by the EU regulatory agencies. The news marks a significant milestone
on the road to getting affordable diagnostic tools into the developing
world".
The group have already launched a rapid test for Chlamydia that is currently
sold within the EU and many other countries around the world. Other tests in the
pipeline include rapid tests for the detection of HIV and influenza.
Charles Gore, president of the World Hepatitis Alliance, commented: "I am
happy this new test has been approved in the EU. Rapid, cheap and robust
diagnostic tests are an important component in the battle to prevent and control
hepatitis B. This is a battle that is only now beginning to be given the
priority it needs with, for the first time, a comprehensive WHO viral hepatitis
resolution on the agenda for the World Health Assembly, which coincides with
World Hepatitis Day on May 19th.'
Source:
Jen Middleton
Wellcome Trust
19 May 2010
Cancer Research UK scientists have discovered sophisticated 'watchman' cells in
humans that can instruct the immune system to destroy foreign invaders like
viruses and cancer cells, according to research published in The Journal of
Experimental Medicine.
The team, based at Cancer Research UK's London Research Institute, examined
human tissues and white blood cells to identify a superior group of dendritic
cells (DC) - key players in the body's defences - in humans for the first time.
'Watchmen' DCs hunt down foreign bodies and flag them up for destruction by T
cells in the immune system. The newly-discovered DCs are better than ordinary
DCs at instructing the T cells to attack and destroy cancer cells and cells
infected with viruses.
This finding opens up opportunities for scientists to investigate the potential
of these superior DCs in the development of new vaccines for many diseases,
including cancer.
Scientists had already discovered a superior subset of DCs in mice, called CD8a+
DC. But until now this group of cells had not been identified in humans.
The team used a new technique* to discover human equivalent DCs** - called
DNGR-1+ DC - in human tissues and developed a method to grow the DNGR-1+
'watchmen' DCs from human blood stem cells.
Lead author, Dr Caetano Reis e Sousa , head of the Immunobiology Laboratory at
Cancer Research UK's London Research Institute, said: "Our discovery is a
crucial step towards harnessing the power of the immune system to fight disease.
"We know these cells are effective 'watchmen' in mice. We now know that
these 'watchmen' also exist in humans, which paves the way for the development
of better vaccines for diseases such as cancer, tuberculosis and HIV infection.
"We're excited to see whether research that follows on from this discovery
will lead to a vaccine we can use to treat cancer patients, but we can't yet say
whether this will be the case."
Dr Lesley Walker, director of cancer information at Cancer Research
"Cancer Research UK is already investing in early clinical trials of
experimental vaccines to treat a range of cancers - including bowel, lung,
breast and pancreatic cancers - and this new discovery will help us develop more
new and efficient ways to target different cancers as effectively as possible
with fewer side effects."
Reference
"Characterization of human DNGR-1+ BDCA3+ leukocytes as putative
equivalents of mouse CD8?+ dendritic cells."
Poulin et al.
JEM.
Notes
* They used a marker molecule called DNGR-1.
** Called CD8a+ DC equivalents - where CD8a+ DC are the mouse DC cells. In
humans the 'equivalents' are called DNGR-1+ human DC.
Source
Cancer Research
18 May 2010
Argos Therapeutics today announced the presentation of data from the Phase 2a
trial of AGS-004, demonstrating that the personalized immunotherapy has a
positive impact on the genetic diversity of residual HIV virus, and also results
in substantially increased time to viral rebound in HIV patients treated with
AGS-004 following antiretroviral therapy (ART) interruption. The data were
discussed in an oral presentation at the 19th Annual Canadian Conference on
HIV/AIDS Research (CAHR), held May 13-16, 2010 in
"We observed viral genetic drift post-ART therapy in several patients, and
in some patients there was a remarkable decrease in viral diversity post-AGS-004
treatment," said Jean-Pierre Routy, M.D., from McGill University Health
Centre in
"The positive clinical outcomes and viral dynamics presented are consistent
with the encouraging interim efficacy data demonstrated in this Phase 2a
trial," said Charles Nicolette, Ph.D., Chief Scientific Officer and Vice
President of Research and Development of Argos Therapeutics. "The efficacy
data, taken with the favorable safety and tolerability profile of AGS-004,
provide a solid rationale for continuing to advance this program into a Phase 2b
trial, which will begin soon."
AGS-004 utilizes autologous RNA encoding HIV antigens Gag, Vpr, Rev and Nef (GVRN).
Genetic evolution of the virus was analyzed through sequencing at least 10
individual clones of each GVRN gene following AGS-004 treatment, and comparing
to those isolated from the pre-treatment sample. Prior data presented from the
Phase 2a trial demonstrated that, as expected, in some subjects, the
post-AGS-004 samples revealed a shift in viral diversity, indicating that the
remaining virus did mutate over the course of treatment.
In the current presentation, clinical outcomes were detailed for patients that
had reached the primary endpoint (three months without ART). According to the
presentation, 17 subjects had completed the three-month ART interruption. The
median time to viral load rebound was four weeks and time to peak viral load was
eight weeks. Eighty-two percent of the patients responded to treatment with
AGS-004, with a mean reduction in viral load of 1.24 log, compared to pre-ART
viral load average. The mean duration of patients' ART interruption was 25.4
weeks. Eight subjects were eligible to continue their treatment interruptions,
14 subjects restarted ART and six subjects had resistance testing completed,
with no evidence of drug resistance. Treatment-related adverse events were
limited to grade 1 or 2 injection site reactions and flu-like or GI symptoms; no
autoimmunity or AIDS-defining events were observed during the study to-date.
The abstract, titled, "AGS-004, an autologous dendritic cell therapy
impacts on the evolution of residual HIV virus along with a substantial increase
in time to viral rebound, during an STI in the CTN 239 clinical study," was
authored by I. Tcherepanova, M.R. Boulassel, A. Carreño, H. Carpenter, M.R.
Loutfy, S. Vezina, C. Tremblay, J. Angel, J. Gill, J. Baril, F Smaill, R. Jain,
D. Healey, T. Chew, C. Nicolette and J.P. Routy.
It is a
plausible explanation 
