BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study

Cortese, Irene; Beck, Erin; Al‐Louzi, Omar; Ohayon, Joan; Andrada, Frances; Osuorah, Ikesinachi; Dwyer, Jenifer; Billioux, Bridgette Jeanne; Dargah-Zada, Nigar; Schindler, Matthew K.; Binder, Kyle W.; Reoma, Lauren B; Norato, Gina; Enose-Akahata, Yoshimi; Smith, Bryan; Monaco, Maria Chiara; Major, Eugene O.; Jacobson, Steven; Stroncek, David F.; Highfill, Steven L.; Panch, Sandhya R.; Reich, Daniel S.; Barrett, John; Nath, Avindra; Muranski, Pawel

doi:10.1016/s1474-4422(21)00174-5

Cited by 42 publications

(34 citation statements)

References 31 publications

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“…The NINDS also issued a Request for Applications entitled “Translational Neural Devices” this year. In the NINDS Division of Intramural Research, ongoing therapeutic studies include immunotherapy trials for the uniformly fatal disorder, progressive multifocal leukoencephalopathy, 16 sensory stimulation as adjunctive rehabilitative therapy for stroke, 17 and gene therapies for disorders of the muscles and nerves. 18,19 A focus on neuroethics has enhanced these studies and the clinical evaluation and use of the therapies they develop.…”

Section: Resultsmentioning

confidence: 99%

Planning and Implementing Strategically

et al. 2022

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At the end of 2020, the National Institute of Neurological Disorders and Stroke, an institute of the National Institutes of Health, completed an 18 month-long strategic planning process that involved and engaged diverse internal and external biomedical and general stakeholders. The Institute published and disseminated its 2021-2026 Strategic Plan online in December 2020. Now, 1 year into its implementation, this progress report presents accomplishments to date, new initiatives and opportunities, and a preview of the metrics and benchmarks we will use to gauge the future progress of the strategic plan’s implementation.

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Section: Resultsmentioning

confidence: 99%

Planning and Implementing Strategically

et al. 2022

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“… 244 As BKV and JC virus are closely related and share several immunogenic proteins, adoptive transfer of allogeneic JC-STs or BKV-STs has also been explored as treatment of PML. 49 , 65 , 76 – 78 , 86 Preliminary, albeit very promising, results of those trials demonstrated safety of the infusion of partially matched VSTs as well as alleviation of clinical symptoms, progressive decline of viral load in cerebrospinal fluid and an unprecedented survival beyond 1 year in a number of PML patients with poor expectation for survival. 49 , 65 , 76 – 78 , 86 …”

Section: Extending the Use Of Psts Beyond The Transplant Settingmentioning

confidence: 99%

“…49,65,76–78,86 Preliminary, albeit very promising, results of those trials demonstrated safety of the infusion of partially matched VSTs as well as alleviation of clinical symptoms, progressive decline of viral load in cerebrospinal fluid and an unprecedented survival beyond 1 year in a number of PML patients with poor expectation for survival. 49,65,76–78,86…”

Section: Extending the Use Of Psts Beyond The Transplant Settingmentioning

confidence: 99%

Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond

et al. 2023

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Adoptive immunotherapy with virus-specific cytotoxic T cells (VSTs) has evolved over the last three decades as a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after solid organ or allogeneic hematopoietic cell-transplantation (allo-HCT). Since the early proof-of-principle studies demonstrating that seropositive donor-derived T cells, specific for the commonest pathogens post transplantation, namely cytomegalovirus or Epstein-Barr virus (EBV) and generated by time-and labor-intensive protocols, could effectively control viral infections, major breakthroughs have then streamlined the manufacturing process of pathogen-specific T cells (pSTs), broadened the breadth of target recognition to even include novel emerging pathogens and enabled off-the-shelf administration or pathogen-naive donor pST production. We herein review the journey of evolution of adoptive immunotherapy with nonengineered, natural pSTs against infections and virus-associated malignancies in the transplant setting and briefly touch upon recent achievements using pSTs outside this context.

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“…Only one patient experienced mild IRIS, and none had transplantation‐related adverse events. 60 , 61 , 62 , 63 , 64 , 65 Thus, allogenic T‐cell transfer appears to be a promising therapeutic strategy in PML related to refractory immunosuppression. However, virus‐specific T‐cell allogenic transfer requires an infrastructure and a technical expertise that are available at only few centers.…”

Section: Restoration Of Immunity As a Treatment For Pmlmentioning

confidence: 99%

Advances in Treatment of Progressive Multifocal Leukoencephalopathy

Bernard‐Valnet

Koralnik

Pasquier

2021

Annals of Neurology

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Progressive multifocal encephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), which occurs in immunocompromised individuals. Management of PML relies on restoration of immunity within the CNS. However, when this restoration cannot be readily achieved, PML has a grim prognosis. Innovative strategies have shown promise in promoting anti‐JCV immune responses, and include T‐cell adoptive transfer or immune checkpoint inhibitor therapies. Conversely, management of immune reconstitution inflammatory syndrome, particularly in iatrogenic PML, remains a major challenge. In this paper, we review recent development in the treatment of PML. ANN NEUROL 2021;90:865–873

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BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study

Cited by 42 publications

References 31 publications

Planning and Implementing Strategically

Planning and Implementing Strategically

Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond

Advances in Treatment of Progressive Multifocal Leukoencephalopathy

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