Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes appeared first on Mayo Clinic News Network.

Mayo Clinic researchers find “sugar coating” cells can protect those typically destroyed in type 1 diabetes

An immunofluorescence microscopy image shows a cluster of insulin-producing beta cells (green) under attack by immune cells (dense cluster of blue dots) in a preclinical model of type 1 diabetes.

ROCHESTER, Minn. — Scientific breakthroughs in one disease don’t always shed light on treating other diseases. But that’s been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it’s possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

Virginia Shapiro, Ph.D.

“Our findings show that it’s possible to engineer beta cells that do not prompt an immune response,” says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro’s team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

“The expression of this enzyme basically ‘sugar coats’ cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response,” Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Justin Choe

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

“Though the beta cells were spared, the immune system remained intact,” Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

“A goal would be to provide transplantable cells without the need for immunosuppression,” says Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

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Mayo Clinic treats first person in the US with a novel radiopharmaceutical therapy for breast cancer

Researchers are leading the nation in using powerful and precise radioactive drugs to treat people with complex cancers.  

ROCHESTER, Minn. — Mayo Clinic has treated the first person in the U.S. using a novel radioactive medicine for advanced breast cancer as part of an international multisite clinical trial.

The medicine used in this clinical trial contains actinium-225, a highly potent alpha-emitting radiopharmaceutical therapy that was first developed for a subtype of gastroenteropancreatic neuroendocrine tumors, which are rare and can form in the pancreas and the gastrointestinal tract. The alpha-emitting radiopharmaceutical therapy is intended to work by passing through the blood to stick to cancer cells, delivering powerful and precise radiation without harming healthy cells.

The Mayo Clinic researchers are the first to apply this therapy in America to a patient with metastatic breast cancer. The phase 1b/2 open-label trial is being conducted at all three academic Mayo Clinic sites in Rochester, Minnesota; Phoenix; Jacksonville, Florida; and approximately 20 other sites across the U.S. The first person treated was at Mayo Clinic in Florida.

Geoffrey Johnson, M.D., Ph.D.

The principal investigator at Mayo Clinic is Geoffrey Johnson, M.D., Ph.D., a professor of radiology and a leader in radiopharmaceutical therapies. He says these are innovative cancer treatments that use radioactive medicines designed to target and kill cancer cells with high precision.

Mayo Clinic has nearly 20 active radiopharmaceutical therapy clinical trials, with 10 more preparing to launch, targeting many different types of cancer. Mayo Clinic in Rochester treats more patients with modern radiopharmaceutical therapies, such as lutetium dotatate for neuroendocrine cancers and lutetium PSMA for prostate cancers, than any other center in the world.

Lutetium dotatate and lutetium PSMA are beta-emitting radiopharmaceuticals. They use beta particles, which are tiny subatomic particles, to radiate at a low level. In contrast, alpha-emitting radiopharmaceuticals use alpha particles that are 8,000 times more massive than beta particles, and travel only three cell diameters after they are emitted from the therapy.

“This means alpha emitters can deliver a much more powerful impact over a shorter distance. If you consider killing a cancer cell is like knocking down a brick wall, then the difference is like throwing a 10-pound dumbbell (beta) at the wall versus a fully loaded Mack truck (alpha),” says Dr. Johnson. “The alpha emitter’s potential lies in its power and in its ability to precisely kill even a single cancer cell without injuring surrounding healthy tissue, making it a next-generation therapy.”

In preclinical studies, data indicates actinium-225 DOTATATE that targets the somatostatin receptor subtype 2expression demonstrated feasibility and potential efficacy for treatment of ER+ metastatic breast cancer in the laboratory. The drug was developed by RayzeBio Inc., a Bristol Myers Squibb Company, the sponsor of the active phase 1b/2 clinical trial.

Study Title: Phase 1b/2 Open-label Trial of 225Ac-DOTATATE (RYZ101) in Subjects with Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-negative, Locally Advanced and Unresectable or Metastatic Breast Cancer Expressing Somatostatin Receptors (SSTRs) and Progressed After Antibody-drug Conjugates And/or Chemotherapy (TRACY-1)

  • Descriptor: Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) alone and with pembrolizumab in subjects with ER+, HER2-negative unresectable or metastatic breast cancer expressing SSTRs.
  • Sponsor: RayzeBio Inc.
  • Link: https://clinicaltrials.gov/study/NCT06590857

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and to providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

The post Mayo Clinic treats first person in the US with a novel radiopharmaceutical therapy for breast cancer appeared first on Mayo Clinic News Network.