Investigators Report the Successful Allogeneic Transfer of Cytotoxic T Lymphocytes in Progressive Multifocal Leukoencephalopathy

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The T cells that were modified ex vivo were made to fight the BK polyomavirus, a genetically similar, immunologic epitope of the JC polyomavirus.
The T cells that were modified ex vivo were made to fight the BK polyomavirus, a genetically similar, immunologic epitope of the JC polyomavirus.

New research conducted by physicians from the University of Texas MD Anderson Cancer Center has revealed that allogeneic adoptive cell therapy (ACT) could have the potential to work effectively and, in 3 patients with different underlying conditions, has appeared to provide a type of “borrowed” immunity that helped clear the virus responsible for progressive multifocal leukoencephalopathy (PML). The results from the study (ClinicalTrials.org Identifier: NCT02479698) were published in the New England Journal of Medicine.1

The T cells that were modified ex vivo were made to fight the BK polyomavirus, a genetically similar, immunologic epitope of the JC polyomavirus; the JC virus is characteristic of PML. The T cells first came from third-party donors, meaning that it is an allogeneic, “off-the-shelf” ACT approach. The patients received BK virus-specific T-cell infusions every 4 weeks at a dose of 2 × 105 T cells per kilogram of body weight until the virus was cleared from the CSF. Patient 1, however, received 2 additional infusions.

Once cryopreserved donor cells were thawed, the researchers closely matched T cell lines for human leukocyte antigen (HLA) to each patient with the idea that this matching could prevent some degree of transplantation rejection.

The 3 patients who received the modified, T-cell-based treatment had different underlying conditions. They included patient 1, a female aged 32 years with acute myeloid leukemia (AML) who had undergone a cord blood transplant; patient 2, a female aged 73 years, with JAK2-positive polycythemia rubra vera (a myeloproliferative disorder) who was on ruxolitinib therapy; and a third male patient, aged 35 years, who had HIV.

The patient with AML was first in remission, but presented with symptoms of PML 20 months after double cord-blood transplantation with myeloablative conditioning for FLT3-positive AML — 13 months after discontinuing prophylaxis for graft-versus-host disease.

Patients 1 and 3 demonstrated clinical improvement with a reduction in the JC virus in their cerebrospinal fluid. “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,” said lead researcher Katy Rezvani, MD, PhD, professor in the department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center in Houston, in a press release accompanying the study.2

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