Off-the-Shelf Third-Party Virus-Specific T Cell Therapy to Treat JC Polyomavirus Infection in Hematopoietic Stem Cell Transplantation Recipients

Rubinstein, Jeremy D.; Jodele, Sonata; Heyenbruch, Daria; Wilhelm, Jamie; Thomas, Scott L.; Lutzko, Carolyn; Zhu, Xin‐Guang; Leemhuis, Tom; Cancelas, José A.; Keller, Michael D.; Bollard, Catherine M.; Hanley, Patrick J.; Boghdadly, Zeinab El; Mims, Alice S.; Davies, Stella M.; Grimley, Michael; Nelson, Adam

doi:10.1016/j.jtct.2021.11.005

Cited by 18 publications

(17 citation statements)

References 27 publications

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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%

“…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][77][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][77][78]86 Human immunodeficiency virus Although antiretroviral therapy (ART) is successfully used to suppress HIV-1 replication, viral latency is responsible for the persistence of a reservoir of infected CD4+ T cells which lead to systemic viremia should ART is ceased, thus constituting major barrier to HIV cure.…”

Section: Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

“…Progressive multifocal leukoencephalopathy (PML) is a devastating and generally fatal neurologic disease occurring in profoundly immunocompromised patients due to brain infection with JC polyomavirus and lacking effective treatment, unless cellular immunity is restored 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%

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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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Section: Extending the Use Of Psts Beyond The Transplant Settingmentioning

confidence: 99%

Section: Extending the Use Of Psts Beyond The Transplant Settingmentioning

confidence: 99%

Section: Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

Section: Extending the Use Of Psts Beyond The Transplant Settingmentioning

confidence: 99%

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

et al. 2023

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“…Because the BKPyV genome has 75% homology to JCPyV [40], some studies have used peptide pools derived from BKPyV. For instance, Rubinstein et al [41 ▪▪ ] used BKPyV-specific off-the-shelf T cells to treat JCPyV PML in two allogeneic HCT recipients. Although one patient demonstrated clinical improvement and viral clearance after six VST infusions, the other patient likely developed an inflammatory immune reconstitution syndrome (IRIS) due to T-cell reconstitution, which was associated with a fatal outcome.…”

Section: Text Of Reviewmentioning

confidence: 99%

Immunocompromised host section: Adoptive T-cell therapy for dsDNA viruses in allogeneic hematopoietic cell transplant recipients

Walti

Stuehler

Palianina

et al. 2022

Current Opinion in Infectious Diseases

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Purpose of review Double-stranded DNA (dsDNA) viruses remain important causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As treatment options are limited, adoptive therapy with virusspecific T cells (VST) is promising in restoring immunity and thereby preventing and treating virus infections. Here we review current evidence and recent advances in the field of VST for dsDNA viruses in allogeneic HCT recipients. Recent findingsFour different protocols for VST generation are currently used in clinical trials, and various products including multivirus-specific and off-the-shelf products are under investigation for prophylaxis, preemptive therapy or treatment. Data from nearly 1400 dsDNA-VST applications in allogeneic HCT patients have been published and demonstrated its safety. Although Epstein--Barr virus, cytomegalovirus, and adenovirusspecific T-cell therapy studies have predominated over the past 25 years, additional human herpes viruses were added to multivirus-specific T cells over the last decade and clinical evidence for polyomavirus-specific VST has just recently emerged. Response rates of around 70--80% have been reported, but cautious interpretation is warranted as data are predominantly from phase 1/2 studies and clinical efficacy needs to be confirmed in phase 3 studies.

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Clinical Experiences with TAA ‐T in Lymphoid Malignancies

Toner–,

Kinoshita–,

Bollard

2024

Precision Cancer Therapies Vol 2 ‐ Immunologic Approaches for the Treatment of Lymphoid Malignancies ‐ From Concept to Practice

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Off-the-Shelf Third-Party Virus-Specific T Cell Therapy to Treat JC Polyomavirus Infection in Hematopoietic Stem Cell Transplantation Recipients

Cited by 18 publications

References 27 publications

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

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

Immunocompromised host section: Adoptive T-cell therapy for dsDNA viruses in allogeneic hematopoietic cell transplant recipients

Clinical Experiences with TAA ‐T in Lymphoid Malignancies

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