Adoptive T-cell therapy treats PML

Image by Marvin 101

Adoptive T-cell therapy has proven effective for treating progressive multifocal leukoencephalopathy (PML), according to research published in The New England Journal of Medicine.

Researchers observed substantial improvements in three PML patients infused with donor T cells targeting the BK virus.

Although one patient ultimately died, two had complete clearance of the JC virus and no clinical signs of PML after treatment.

“The JC and BK viruses are genetically similar and share proteins that can be targeted by the immune system,” said study author Katy Rezvani, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

“Because of these similarities, we hypothesized that T cells developed against BK virus may also be effective against JC virus infection.”

Dr. Rezvani’s team developed a novel approach for the generation of BK virus-specific T cells from healthy donors and established a bank of viral-specific T cells for immediate clinical use.

The researchers treated three patients with third-party, partially human leukocyte antigen (HLA)-matched, BK virus-specific T cells.

Patient 1 was a 32-year-old female with acute myeloid leukemia (AML) who previously received a double cord blood transplant.

Patient 2 was a 73-year-old female with JAK2-positive polycythemia rubra vera (PV) who had been treated with ruxolitinib.

Patient 3 was a 35-year-old man with AIDS who had discontinued highly active antiretroviral therapy due to side effects and who was no longer able to walk.

Following the first infusion, all three patients had a reduction in JC viral load in their cerebrospinal fluid. Viral loads dropped from:

• 700 to 78 copies in the AML patient
• 230,000 to 5,200 in the PV patient
• 4,300 to 1,300 in the AIDS patient.

“After infusion of viral-specific T cells, patients 1 and 3 had clinical improvement with significant reduction in JC virus in their cerebrospinal fluid,” Dr. Rezvani said.

“Both patients responded despite persistent T-cell immunodeficiency, supporting the concept that the response was mediated by the adoptively infused viral-specific T cells, and there were no infusion-related reactions.”

The AML patient received two additional infusions, which resulted in clearance of the virus in the cerebrospinal fluid and no signs of PML 27 months after the first infusion.

The PV patient received a second infusion that further reduced JC viral load, but no additional improvement was seen. The patient died 8 months after the first infusion.

The AIDS patient received additional infusions, resulting in complete clearance of the JC virus. This patient has regained mobility, and, 9 months after the first infusion, he is able to walk with a cane.

“We are encouraged that off-the-shelf, third-party, partially HLA-matched BK viral-specific T cells may provide a therapy for PML,” Dr. Rezvani said. “Further study in a larger group of patients is required to determine the success rate, durability, and longer-term adverse events with this treatment.”

This study was supported with funding from the Myelodysplastic Syndromes and Acute Myeloid Leukemia Moon Shot, part of MD Anderson’s Moon Shots Program, as well as the National Institutes of Health.

Image by Marvin 101

Adoptive T-cell therapy has proven effective for treating progressive multifocal leukoencephalopathy (PML), according to research published in The New England Journal of Medicine.

Researchers observed substantial improvements in three PML patients infused with donor T cells targeting the BK virus.

Although one patient ultimately died, two had complete clearance of the JC virus and no clinical signs of PML after treatment.

“The JC and BK viruses are genetically similar and share proteins that can be targeted by the immune system,” said study author Katy Rezvani, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

“Because of these similarities, we hypothesized that T cells developed against BK virus may also be effective against JC virus infection.”

Dr. Rezvani’s team developed a novel approach for the generation of BK virus-specific T cells from healthy donors and established a bank of viral-specific T cells for immediate clinical use.

The researchers treated three patients with third-party, partially human leukocyte antigen (HLA)-matched, BK virus-specific T cells.

Patient 1 was a 32-year-old female with acute myeloid leukemia (AML) who previously received a double cord blood transplant.

Patient 2 was a 73-year-old female with JAK2-positive polycythemia rubra vera (PV) who had been treated with ruxolitinib.

Patient 3 was a 35-year-old man with AIDS who had discontinued highly active antiretroviral therapy due to side effects and who was no longer able to walk.

Following the first infusion, all three patients had a reduction in JC viral load in their cerebrospinal fluid. Viral loads dropped from:

• 700 to 78 copies in the AML patient
• 230,000 to 5,200 in the PV patient
• 4,300 to 1,300 in the AIDS patient.

“After infusion of viral-specific T cells, patients 1 and 3 had clinical improvement with significant reduction in JC virus in their cerebrospinal fluid,” Dr. Rezvani said.

“Both patients responded despite persistent T-cell immunodeficiency, supporting the concept that the response was mediated by the adoptively infused viral-specific T cells, and there were no infusion-related reactions.”

The AML patient received two additional infusions, which resulted in clearance of the virus in the cerebrospinal fluid and no signs of PML 27 months after the first infusion.

The PV patient received a second infusion that further reduced JC viral load, but no additional improvement was seen. The patient died 8 months after the first infusion.

The AIDS patient received additional infusions, resulting in complete clearance of the JC virus. This patient has regained mobility, and, 9 months after the first infusion, he is able to walk with a cane.

“We are encouraged that off-the-shelf, third-party, partially HLA-matched BK viral-specific T cells may provide a therapy for PML,” Dr. Rezvani said. “Further study in a larger group of patients is required to determine the success rate, durability, and longer-term adverse events with this treatment.”

This study was supported with funding from the Myelodysplastic Syndromes and Acute Myeloid Leukemia Moon Shot, part of MD Anderson’s Moon Shots Program, as well as the National Institutes of Health.

Image by Marvin 101

Adoptive T-cell therapy has proven effective for treating progressive multifocal leukoencephalopathy (PML), according to research published in The New England Journal of Medicine.

Researchers observed substantial improvements in three PML patients infused with donor T cells targeting the BK virus.

Although one patient ultimately died, two had complete clearance of the JC virus and no clinical signs of PML after treatment.

“The JC and BK viruses are genetically similar and share proteins that can be targeted by the immune system,” said study author Katy Rezvani, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

“Because of these similarities, we hypothesized that T cells developed against BK virus may also be effective against JC virus infection.”

Dr. Rezvani’s team developed a novel approach for the generation of BK virus-specific T cells from healthy donors and established a bank of viral-specific T cells for immediate clinical use.

The researchers treated three patients with third-party, partially human leukocyte antigen (HLA)-matched, BK virus-specific T cells.

Patient 1 was a 32-year-old female with acute myeloid leukemia (AML) who previously received a double cord blood transplant.

Patient 2 was a 73-year-old female with JAK2-positive polycythemia rubra vera (PV) who had been treated with ruxolitinib.

Patient 3 was a 35-year-old man with AIDS who had discontinued highly active antiretroviral therapy due to side effects and who was no longer able to walk.

Following the first infusion, all three patients had a reduction in JC viral load in their cerebrospinal fluid. Viral loads dropped from:

• 700 to 78 copies in the AML patient
• 230,000 to 5,200 in the PV patient
• 4,300 to 1,300 in the AIDS patient.

“After infusion of viral-specific T cells, patients 1 and 3 had clinical improvement with significant reduction in JC virus in their cerebrospinal fluid,” Dr. Rezvani said.

“Both patients responded despite persistent T-cell immunodeficiency, supporting the concept that the response was mediated by the adoptively infused viral-specific T cells, and there were no infusion-related reactions.”

The AML patient received two additional infusions, which resulted in clearance of the virus in the cerebrospinal fluid and no signs of PML 27 months after the first infusion.

The PV patient received a second infusion that further reduced JC viral load, but no additional improvement was seen. The patient died 8 months after the first infusion.

The AIDS patient received additional infusions, resulting in complete clearance of the JC virus. This patient has regained mobility, and, 9 months after the first infusion, he is able to walk with a cane.

“We are encouraged that off-the-shelf, third-party, partially HLA-matched BK viral-specific T cells may provide a therapy for PML,” Dr. Rezvani said. “Further study in a larger group of patients is required to determine the success rate, durability, and longer-term adverse events with this treatment.”

This study was supported with funding from the Myelodysplastic Syndromes and Acute Myeloid Leukemia Moon Shot, part of MD Anderson’s Moon Shots Program, as well as the National Institutes of Health.