Low-dose T-cell transfer can fight CMV

Micrograph showing

CMV infection

A new study indicates that transferring low doses of immune cells may be sufficient to protect against cytomegalovirus (CMV) infection in patients receiving allogeneic stem cell transplant.

The researchers noted that the adoptive transfer of donor-derived, virus-specific, memory T cells is a promising strategy for treating and preventing CMV infection.

But transferring too many of these cells can increase the risk of graft-vs-host disease.

So Christian Stemberger, PhD, of Technische Universitaet Muenchen in Germany, and his colleagues set out to establish a lower limit for successful adoptive T-cell therapy.

The team reported their results—observed in mice and 2 human patients—in Blood.

The researchers first conducted low-dose CD8+ T-cell transfers in the murine Listeria monocytogenes infection model.

And they found these MHC-Streptamer-enriched, antigen-specific, CD62L^hi, CD8⁺ memory T cells proliferated, differentiated, and protected against Listeria monocytogenes infections.

“The most astonishing result was that the offspring cells of just 1 transferred donor cell were enough to completely protect the animals,” Dr Stemberger said.

Next, the researchers used virus-specific T cells to treat 2 critically ill pediatric patients—1 with severe combined immunodeficiency (SCID) and the other with B-cell acute lymphoblastic leukemia.

The patients had received allogeneic transplants and subsequently developed CMV infections.

The patients received low-dose transfers of Streptamer-enriched, CMV-specific, CD8⁺ T cells—3750 cells per kilogram of body weight for the SCID patient and 5130 cells per kilogram of body weight for the leukemia patient.

In both patients, the researchers observed “strong, pathogen-specific T-cell expansion.” The CMV-specific, CD8⁺ T cells proliferated, and the CMV viral load decreased. Furthermore, neither patient developed graft-vs-host disease.

“It is a great advantage that even just a few cells can provide protection [from CMV],” said study author Michael Neuenhahn, Dr med, also of Technische Universitaet Muenchen.

“This means that the cells can be used for preventive treatment in low doses that are gentler on the organism.”

The researchers are now testing the potential of the CMV-specific, CD8⁺ T cells in a clinical study.

Micrograph showing

CMV infection

A new study indicates that transferring low doses of immune cells may be sufficient to protect against cytomegalovirus (CMV) infection in patients receiving allogeneic stem cell transplant.

The researchers noted that the adoptive transfer of donor-derived, virus-specific, memory T cells is a promising strategy for treating and preventing CMV infection.

But transferring too many of these cells can increase the risk of graft-vs-host disease.

So Christian Stemberger, PhD, of Technische Universitaet Muenchen in Germany, and his colleagues set out to establish a lower limit for successful adoptive T-cell therapy.

The team reported their results—observed in mice and 2 human patients—in Blood.

The researchers first conducted low-dose CD8+ T-cell transfers in the murine Listeria monocytogenes infection model.

And they found these MHC-Streptamer-enriched, antigen-specific, CD62L^hi, CD8⁺ memory T cells proliferated, differentiated, and protected against Listeria monocytogenes infections.

“The most astonishing result was that the offspring cells of just 1 transferred donor cell were enough to completely protect the animals,” Dr Stemberger said.

Next, the researchers used virus-specific T cells to treat 2 critically ill pediatric patients—1 with severe combined immunodeficiency (SCID) and the other with B-cell acute lymphoblastic leukemia.

The patients had received allogeneic transplants and subsequently developed CMV infections.

The patients received low-dose transfers of Streptamer-enriched, CMV-specific, CD8⁺ T cells—3750 cells per kilogram of body weight for the SCID patient and 5130 cells per kilogram of body weight for the leukemia patient.

In both patients, the researchers observed “strong, pathogen-specific T-cell expansion.” The CMV-specific, CD8⁺ T cells proliferated, and the CMV viral load decreased. Furthermore, neither patient developed graft-vs-host disease.

“It is a great advantage that even just a few cells can provide protection [from CMV],” said study author Michael Neuenhahn, Dr med, also of Technische Universitaet Muenchen.

“This means that the cells can be used for preventive treatment in low doses that are gentler on the organism.”

The researchers are now testing the potential of the CMV-specific, CD8⁺ T cells in a clinical study.

Micrograph showing

CMV infection

A new study indicates that transferring low doses of immune cells may be sufficient to protect against cytomegalovirus (CMV) infection in patients receiving allogeneic stem cell transplant.

The researchers noted that the adoptive transfer of donor-derived, virus-specific, memory T cells is a promising strategy for treating and preventing CMV infection.

But transferring too many of these cells can increase the risk of graft-vs-host disease.

So Christian Stemberger, PhD, of Technische Universitaet Muenchen in Germany, and his colleagues set out to establish a lower limit for successful adoptive T-cell therapy.

The team reported their results—observed in mice and 2 human patients—in Blood.

The researchers first conducted low-dose CD8+ T-cell transfers in the murine Listeria monocytogenes infection model.

And they found these MHC-Streptamer-enriched, antigen-specific, CD62L^hi, CD8⁺ memory T cells proliferated, differentiated, and protected against Listeria monocytogenes infections.

“The most astonishing result was that the offspring cells of just 1 transferred donor cell were enough to completely protect the animals,” Dr Stemberger said.

Next, the researchers used virus-specific T cells to treat 2 critically ill pediatric patients—1 with severe combined immunodeficiency (SCID) and the other with B-cell acute lymphoblastic leukemia.

The patients had received allogeneic transplants and subsequently developed CMV infections.

The patients received low-dose transfers of Streptamer-enriched, CMV-specific, CD8⁺ T cells—3750 cells per kilogram of body weight for the SCID patient and 5130 cells per kilogram of body weight for the leukemia patient.

In both patients, the researchers observed “strong, pathogen-specific T-cell expansion.” The CMV-specific, CD8⁺ T cells proliferated, and the CMV viral load decreased. Furthermore, neither patient developed graft-vs-host disease.

“It is a great advantage that even just a few cells can provide protection [from CMV],” said study author Michael Neuenhahn, Dr med, also of Technische Universitaet Muenchen.

“This means that the cells can be used for preventive treatment in low doses that are gentler on the organism.”

The researchers are now testing the potential of the CMV-specific, CD8⁺ T cells in a clinical study.