Posted by
Happy Mum to be
comments (0)
New HIV model suggests killer T cell for vaccine
April 29, 2010
Limited success in modelling the behaviour of the complex, unusual and unpredictable HIV virus has slowed efforts to develop an effective vaccine to prevent AIDS.
A new improved modelling system, developed by Chinese researchers, which attempts to incorporate more of the virus' random behavioural dynamics, suggests that a particular type of T cell could be useful in the development of an AIDS vaccine.
New research published today, Thursday 29 April, in New Journal of Physics (co-owned by the Institute of Physics and German Physical Society), describes how physicists and biologists from Xiamen University have been able to incorporate random patterns in the virus' mutation, and the way the virus responds to antibodies, into their model.
Gratifyingly, they have found that the new model, and the projections made by the new model for development of disease, mirror real-life, clinical behaviour of the virus.
Clinical trials show that the HIV virus behaves quite normally during the acute first phase of human infection, normally 2-6 weeks after HIV enters the host body, during which time the strength of the virus increases and our immune systems deploy killer T cells, CD4+ T cells, to battle against it.
Outwardly, we would experience flu like symptoms and would, when we started to feel better, imagine that we are over the infection but this is not so with the HIV virus which somehow avoids total annihilation and manages to spend years rebuilding strength, slowly chipping away at our immune system.
Researchers suspect that HIV's ability to avoid annihilation has to do with its own mutating properties and its ability to preferentially target CD4+ T cells, the master regulators of our immune system.
The model-makers from Xiamen University have created a simulation which takes a wider range of variables into consideration and while they are in agreement that both HIV's mutating and T-cell targeting ability are crucial to the virus' devastating success rate, they have found a possible chink in the virus' armour.
To date, no models have been able to discern between the behavioural patterns of two different types of T-cells, both of which are involved in our internal fights against HIV.
These are CD4+ T and CD8+ T cells. Patterns emerging from these new models now suggest that CD8+T cells could be used to stimulate a stronger response against the virus.
This particular type of T-cell does not appear to be as preferentially targeted by HIV as its counterpart and also appears to be more actively involved in putting the virus down during the first acute phase of the infection.
As the researchers write, "We assess the relative importance of various immune system components in acute phase and have found that the CD8+ T cells play a decisive role to suppress the viral load. This observation implies that stimulation of a CD8+T cell response might be an important goal in the development of an effective vaccine against AIDS."
Institute of Physics
MU researchers show potential for new cancer detection and therapy method
April 23, 2010
University of Missouri School of Medicine scientists explain a potentially new early cancer detection and treatment method using nanoparticles created at MU in an article published in the Proceedings of the National Academy of Sciences. The article illustrates how engineered gold nanoparticles tied to a cancer-specific receptor could be targeted to tumor cells to treat prostate, breast or lung cancers in humans.
"When injected into the body, the Gastrin Releasing Peptide (GRP) cancer receptor serves as a signaling device to the gold nanoparticle, which allows for targeted delivery to the tumor site," said Kattesh Katti, PhD, who wrote the article with Raghuraman Kannan, PhD. "Consequently, the radiotherapeutic properties of such nanoparticles also provides valuable imaging and therapeutic tools that can be used for early cancer detection and therapy in various human cancers."
Because GRP receptor mediated imaging and the radiotherapy specifically targets cancer cells, patients could benefit from a more effective treatment with fewer side effects. GRP receptors are abundant in prostate, breast and small lung cancer cells, and the effectiveness of Katti and Kannan's gold nanoparticles has been proved in numerous studies.
"The development of GRP-receptor specific gold nanoparticles and proof of cancer receptor specificity in living subjects, as described by Drs. Katti and Kannan, is a significant and critical step toward the utility of engineered gold nanoparticles in molecular imaging and therapy of various cancers," said Institute of Medicine member Sanjiv Sam Gambhir, MD, PhD, Virginia and D. K. Ludwig Professor, as well as director of the Molecular Imaging Program and Canary Center for Cancer Early Detection at Stanford University.
Katti, Kannan, and others with the MU School of Medicine Department of Radiology have been researching the development of tumor specific gold nanoparticles for more than five years.
"This discovery presents a plethora of realistic opportunities for clinical translation, not only in the development of nanomedicine-based diagnostic technologies for early stage detection but also for therapies for treating tumors in prostate, breast and small cell lung cancer," Kannan said.
Kannan and Katti have developed a library of more than 85 engineered nanoparticles for use in molecular imaging and therapy. With scientists at the MU Research Reactor (MURR), the most powerful university reactor in the world, they have developed cancer specific therapeutic radioactive gold nanoparticles. MURR is one of only a few sites worldwide able to produce cancer targeting gold nanoparticles.
University of Missouri-Columbia
Researchers use novel nanoparticle vaccine to cure type 1 diabetes in mice
April 09, 2010
Using a sophisticated nanotechnology-based "vaccine," researchers were able to successfully cure mice with type 1 diabetes and slow the onset of the disease in mice at risk for the disease. The study, co-funded by the Juvenile Diabetes Research Foundation, provides new and important insights into understanding how to stop the immune attack that causes type 1 diabetes, and could even have implications for other autoimmune diseases.
The study, conducted at the University of Calgary in Alberta, Canada, was published today in the online edition of the scientific journal Immunity.
The research was led by Dr. Pere Santamaria from the Julia McFarlane Diabetes Researchers Center at the University of Calgary, Alberta. The researchers were looking to specifically stop the autoimmune response that causes type 1 diabetes without damaging the immune cells that provide protection against infections - what is called an "antigen-specific" immunotherapy. Type 1 diabetes is caused when certain white blood cells (called T cells) mistakenly attack and destroy the insulin-producing beta cells in the pancreas.
Antigen-specific immunotherapies, like Dr. Santamaria's work on nanovaccines, are a priority within JDRF's Immune Therapies program.
"Essentially there is an internal tug-of-war between aggressive T-cells that want to cause the disease and weaker T cells that want to stop it from occurring," said Dr. Santamaria, who is a JDRF Scholar - a research award to academic scientists taking innovative and creative approaches to better treating and curing type 1 diabetes and its complications.
The researchers developed a unique vaccine comprised of nanoparticles, which are thousands of times smaller than the size of a cell. These nanoparticles are coated with protein fragments - peptides - specific to type 1 diabetes that are bound to molecules (MHC molecules) that play a critical role in presenting peptides to T cells. The nanoparticle vaccine worked by expanding the number of peptide-specific regulatory T cells that suppressed the aggressive immune attack that destroys beta cells. The expanded peptide-specific regulatory cells shut down the autoimmune attack by preventing aggressive autoimmune cells from being stimulated by either the peptide contained in the vaccine or by any other type 1 diabetes autoantigen presented simultaneously on the same antigen presenting cell.
The research also provided an important insight into the ability to translate these findings in mice into therapeutics for people with diabetes: nanoparticles that contained human diabetes-related molecules were able to restore normal blood sugar levels in a humanized mouse model of diabetes.
According to Teodora Staeva, Ph.D., JDRF Program Director of Immune Therapies, a key finding from the Alberta study is that only the immune cells specifically focused on aggressively destroying beta cells (or, alternatively, regulating these cells) responded to the antigen-specific nanoparticle vaccine. That means the treatment did not compromise the rest of the immune system - a key consideration for the treatment to be safe and effective in an otherwise healthy person with type 1 diabetes. "The potential that nanoparticle vaccine therapy holds in reversing the immune attack without generally suppressing the immune system is significant," said Dr. Staeva. "Dr. Santamaria's research has provided both insight into pathways for developing new immunotherapies and proof-of-concept of a specific therapy that exploits these pathways for preventing and reversing type 1 diabetes."
Dr. Santamaria noted that the study had implications for other autoimmune diseases beyond type 1 diabetes. "If the paradigm on which this nanovaccine is based holds true in other chronic autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and others, nanovaccines might find general applicability in autoimmunity," he said.
The nanoparticle vaccine technology used in the study has been licensed by Parvus Therapeutics, Inc., a biotechnology company arising from the University Technology International LP, the technology transfer and commercialization center for the University of Calgary. Parvus Therapeutics is focused on the development and commercialization of the nanotechnology-based therapeutic platform for the potential treatment of type 1 diabetes.
Juvenile Diabetes Research Foundation International
Nanoparticle-delivered 'suicide' genes slowed ovarian tumor growth
July 30, 2009
PHILADELPHIA - Nanoparticle delivery of diphtheria toxin-encoding DNA selectively expressed in ovarian cancer cells reduced the burden of ovarian tumors in mice, and researchers expect this therapy could be tested in humans within 18 to 24 months, according to a report in Cancer Research, a journal of the American Association for Cancer Research.
Although early stage ovarian cancer can be treated with a combination of surgery followed by chemotherapy, there are currently no effective treatments for advanced ovarian cancer that has recurred after surgery and primary chemotherapy. Therefore, the majority of treated early stage cancers will relapse.
"This report is definitely a reason to hope. We now have a potential new therapy for the treatment of advanced ovarian cancer that has promise for targeting tumor cells and leaving healthy cells healthy," said lead researcher Janet Sawicki, Ph.D., a professor at the Lankenau Institute for Medical Research.
Sawicki and colleagues at the Massachusetts Institute of Technology evaluated the therapeutic efficacy of a cationic biodegradable beta-amino ester polymer as a vector for the nanoparticle delivery of a DNA encoding diphtheria toxin suicide gene. These nanoparticles were injected into mice with primary or metastatic ovarian tumors.
To test the efficacy of this technique, the researchers measured tumor volume before and after treatment. They found that while treated tumors increased 2-fold, this was significantly less than the between 4.1-fold and 6-fold increase in control mice.
Furthermore, four of the treated tumors failed to grow at all, while all control tumors increased in size. Administration of nanoparticles to three different ovarian cancer mouse models prolonged lifespan by nearly four weeks and suppressed tumor growth more effectively, and with minimal non-specific cytotoxicity, than in mice treated with clinically relevant doses of cisplatin and paclitaxel.
Edward Sausville, M.D., Ph.D., an associate editor of Cancer Research and associate director for clinical research at the Greenebaum Cancer Center at the University of Maryland, said this report illustrates significant progress in targeted therapy.
"In oncology we have been studying ways to kill tumors for a long time, but much of this has run up against the real estate principle of location, location, location," he said. "In other words, an effective therapy is not effective if it cannot get to the target."
Sausville said a major accomplishment of this research is the multiple ways it can target ovarian cancer cells, as scientists were able to deliver diphtheria toxin genes, using a nanoparticle, to the actual tumor site (peritoneum) with a basis for selective activity in the cancer cells (how the toxin genes were regulated once inside the cells).
"A real plus of a cancer therapy like this is not just the functionality of the nanoparticle construct molecule, but the ability to deliver the toxin to the tumor cells," said Sausville, who agrees that inception of clinical trials could be just 18 months away.
American Association for Cancer Research
April 29, 2010
Limited success in modelling the behaviour of the complex, unusual and unpredictable HIV virus has slowed efforts to develop an effective vaccine to prevent AIDS.
A new improved modelling system, developed by Chinese researchers, which attempts to incorporate more of the virus' random behavioural dynamics, suggests that a particular type of T cell could be useful in the development of an AIDS vaccine.
New research published today, Thursday 29 April, in New Journal of Physics (co-owned by the Institute of Physics and German Physical Society), describes how physicists and biologists from Xiamen University have been able to incorporate random patterns in the virus' mutation, and the way the virus responds to antibodies, into their model.
Gratifyingly, they have found that the new model, and the projections made by the new model for development of disease, mirror real-life, clinical behaviour of the virus.
Clinical trials show that the HIV virus behaves quite normally during the acute first phase of human infection, normally 2-6 weeks after HIV enters the host body, during which time the strength of the virus increases and our immune systems deploy killer T cells, CD4+ T cells, to battle against it.
Outwardly, we would experience flu like symptoms and would, when we started to feel better, imagine that we are over the infection but this is not so with the HIV virus which somehow avoids total annihilation and manages to spend years rebuilding strength, slowly chipping away at our immune system.
Researchers suspect that HIV's ability to avoid annihilation has to do with its own mutating properties and its ability to preferentially target CD4+ T cells, the master regulators of our immune system.
The model-makers from Xiamen University have created a simulation which takes a wider range of variables into consideration and while they are in agreement that both HIV's mutating and T-cell targeting ability are crucial to the virus' devastating success rate, they have found a possible chink in the virus' armour.
To date, no models have been able to discern between the behavioural patterns of two different types of T-cells, both of which are involved in our internal fights against HIV.
These are CD4+ T and CD8+ T cells. Patterns emerging from these new models now suggest that CD8+T cells could be used to stimulate a stronger response against the virus.
This particular type of T-cell does not appear to be as preferentially targeted by HIV as its counterpart and also appears to be more actively involved in putting the virus down during the first acute phase of the infection.
As the researchers write, "We assess the relative importance of various immune system components in acute phase and have found that the CD8+ T cells play a decisive role to suppress the viral load. This observation implies that stimulation of a CD8+T cell response might be an important goal in the development of an effective vaccine against AIDS."
Institute of Physics
MU researchers show potential for new cancer detection and therapy method
April 23, 2010
University of Missouri School of Medicine scientists explain a potentially new early cancer detection and treatment method using nanoparticles created at MU in an article published in the Proceedings of the National Academy of Sciences. The article illustrates how engineered gold nanoparticles tied to a cancer-specific receptor could be targeted to tumor cells to treat prostate, breast or lung cancers in humans.
"When injected into the body, the Gastrin Releasing Peptide (GRP) cancer receptor serves as a signaling device to the gold nanoparticle, which allows for targeted delivery to the tumor site," said Kattesh Katti, PhD, who wrote the article with Raghuraman Kannan, PhD. "Consequently, the radiotherapeutic properties of such nanoparticles also provides valuable imaging and therapeutic tools that can be used for early cancer detection and therapy in various human cancers."
Because GRP receptor mediated imaging and the radiotherapy specifically targets cancer cells, patients could benefit from a more effective treatment with fewer side effects. GRP receptors are abundant in prostate, breast and small lung cancer cells, and the effectiveness of Katti and Kannan's gold nanoparticles has been proved in numerous studies.
"The development of GRP-receptor specific gold nanoparticles and proof of cancer receptor specificity in living subjects, as described by Drs. Katti and Kannan, is a significant and critical step toward the utility of engineered gold nanoparticles in molecular imaging and therapy of various cancers," said Institute of Medicine member Sanjiv Sam Gambhir, MD, PhD, Virginia and D. K. Ludwig Professor, as well as director of the Molecular Imaging Program and Canary Center for Cancer Early Detection at Stanford University.
Katti, Kannan, and others with the MU School of Medicine Department of Radiology have been researching the development of tumor specific gold nanoparticles for more than five years.
"This discovery presents a plethora of realistic opportunities for clinical translation, not only in the development of nanomedicine-based diagnostic technologies for early stage detection but also for therapies for treating tumors in prostate, breast and small cell lung cancer," Kannan said.
Kannan and Katti have developed a library of more than 85 engineered nanoparticles for use in molecular imaging and therapy. With scientists at the MU Research Reactor (MURR), the most powerful university reactor in the world, they have developed cancer specific therapeutic radioactive gold nanoparticles. MURR is one of only a few sites worldwide able to produce cancer targeting gold nanoparticles.
University of Missouri-Columbia
Researchers use novel nanoparticle vaccine to cure type 1 diabetes in mice
April 09, 2010
Using a sophisticated nanotechnology-based "vaccine," researchers were able to successfully cure mice with type 1 diabetes and slow the onset of the disease in mice at risk for the disease. The study, co-funded by the Juvenile Diabetes Research Foundation, provides new and important insights into understanding how to stop the immune attack that causes type 1 diabetes, and could even have implications for other autoimmune diseases.
The study, conducted at the University of Calgary in Alberta, Canada, was published today in the online edition of the scientific journal Immunity.
The research was led by Dr. Pere Santamaria from the Julia McFarlane Diabetes Researchers Center at the University of Calgary, Alberta. The researchers were looking to specifically stop the autoimmune response that causes type 1 diabetes without damaging the immune cells that provide protection against infections - what is called an "antigen-specific" immunotherapy. Type 1 diabetes is caused when certain white blood cells (called T cells) mistakenly attack and destroy the insulin-producing beta cells in the pancreas.
Antigen-specific immunotherapies, like Dr. Santamaria's work on nanovaccines, are a priority within JDRF's Immune Therapies program.
"Essentially there is an internal tug-of-war between aggressive T-cells that want to cause the disease and weaker T cells that want to stop it from occurring," said Dr. Santamaria, who is a JDRF Scholar - a research award to academic scientists taking innovative and creative approaches to better treating and curing type 1 diabetes and its complications.
The researchers developed a unique vaccine comprised of nanoparticles, which are thousands of times smaller than the size of a cell. These nanoparticles are coated with protein fragments - peptides - specific to type 1 diabetes that are bound to molecules (MHC molecules) that play a critical role in presenting peptides to T cells. The nanoparticle vaccine worked by expanding the number of peptide-specific regulatory T cells that suppressed the aggressive immune attack that destroys beta cells. The expanded peptide-specific regulatory cells shut down the autoimmune attack by preventing aggressive autoimmune cells from being stimulated by either the peptide contained in the vaccine or by any other type 1 diabetes autoantigen presented simultaneously on the same antigen presenting cell.
The research also provided an important insight into the ability to translate these findings in mice into therapeutics for people with diabetes: nanoparticles that contained human diabetes-related molecules were able to restore normal blood sugar levels in a humanized mouse model of diabetes.
According to Teodora Staeva, Ph.D., JDRF Program Director of Immune Therapies, a key finding from the Alberta study is that only the immune cells specifically focused on aggressively destroying beta cells (or, alternatively, regulating these cells) responded to the antigen-specific nanoparticle vaccine. That means the treatment did not compromise the rest of the immune system - a key consideration for the treatment to be safe and effective in an otherwise healthy person with type 1 diabetes. "The potential that nanoparticle vaccine therapy holds in reversing the immune attack without generally suppressing the immune system is significant," said Dr. Staeva. "Dr. Santamaria's research has provided both insight into pathways for developing new immunotherapies and proof-of-concept of a specific therapy that exploits these pathways for preventing and reversing type 1 diabetes."
Dr. Santamaria noted that the study had implications for other autoimmune diseases beyond type 1 diabetes. "If the paradigm on which this nanovaccine is based holds true in other chronic autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and others, nanovaccines might find general applicability in autoimmunity," he said.
The nanoparticle vaccine technology used in the study has been licensed by Parvus Therapeutics, Inc., a biotechnology company arising from the University Technology International LP, the technology transfer and commercialization center for the University of Calgary. Parvus Therapeutics is focused on the development and commercialization of the nanotechnology-based therapeutic platform for the potential treatment of type 1 diabetes.
Juvenile Diabetes Research Foundation International
Nanoparticle-delivered 'suicide' genes slowed ovarian tumor growth
July 30, 2009
PHILADELPHIA - Nanoparticle delivery of diphtheria toxin-encoding DNA selectively expressed in ovarian cancer cells reduced the burden of ovarian tumors in mice, and researchers expect this therapy could be tested in humans within 18 to 24 months, according to a report in Cancer Research, a journal of the American Association for Cancer Research.
Although early stage ovarian cancer can be treated with a combination of surgery followed by chemotherapy, there are currently no effective treatments for advanced ovarian cancer that has recurred after surgery and primary chemotherapy. Therefore, the majority of treated early stage cancers will relapse.
"This report is definitely a reason to hope. We now have a potential new therapy for the treatment of advanced ovarian cancer that has promise for targeting tumor cells and leaving healthy cells healthy," said lead researcher Janet Sawicki, Ph.D., a professor at the Lankenau Institute for Medical Research.
Sawicki and colleagues at the Massachusetts Institute of Technology evaluated the therapeutic efficacy of a cationic biodegradable beta-amino ester polymer as a vector for the nanoparticle delivery of a DNA encoding diphtheria toxin suicide gene. These nanoparticles were injected into mice with primary or metastatic ovarian tumors.
To test the efficacy of this technique, the researchers measured tumor volume before and after treatment. They found that while treated tumors increased 2-fold, this was significantly less than the between 4.1-fold and 6-fold increase in control mice.
Furthermore, four of the treated tumors failed to grow at all, while all control tumors increased in size. Administration of nanoparticles to three different ovarian cancer mouse models prolonged lifespan by nearly four weeks and suppressed tumor growth more effectively, and with minimal non-specific cytotoxicity, than in mice treated with clinically relevant doses of cisplatin and paclitaxel.
Edward Sausville, M.D., Ph.D., an associate editor of Cancer Research and associate director for clinical research at the Greenebaum Cancer Center at the University of Maryland, said this report illustrates significant progress in targeted therapy.
"In oncology we have been studying ways to kill tumors for a long time, but much of this has run up against the real estate principle of location, location, location," he said. "In other words, an effective therapy is not effective if it cannot get to the target."
Sausville said a major accomplishment of this research is the multiple ways it can target ovarian cancer cells, as scientists were able to deliver diphtheria toxin genes, using a nanoparticle, to the actual tumor site (peritoneum) with a basis for selective activity in the cancer cells (how the toxin genes were regulated once inside the cells).
"A real plus of a cancer therapy like this is not just the functionality of the nanoparticle construct molecule, but the ability to deliver the toxin to the tumor cells," said Sausville, who agrees that inception of clinical trials could be just 18 months away.
American Association for Cancer Research
