Cytomegalovirus-Specific T-Cell Transfer for Refractory Cytomegalovirus Infection After Haploidentical Stem Cell Transplantation: The Quantitative and Qualitative Immune Recovery for Cytomegalovirus

Pei, Xu‐Ying; Zhao, Xiang‐Yu; Chang, Ying‐Jun; Liu, Jing; Xu, Lei; Wang, Yu; Zhang, Xiao-Hui; Wang, Han; Chen, Yuhong; Huang, Xiao‐Jun

doi:10.1093/infdis/jix357

Cited by 87 publications

(66 citation statements)

References 35 publications

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“…Adoptive transfer of ex vivo generated CMV‐specific T lymphocytes (CMV‐CTL) has the potential to restore immunity, prevent CMV, and circumvent the need for pharmacologic therapies . The main results of trials of CMV‐CTL therapy for CMV infection in allo‐HSCT recipients published in the last 5 years are described in Table . Overall, these studies showed that CMV‐CTL therapy was safe, not associated with an increase in GVHD and associated with a reduction in the viral burden.…”

Section: Resultsmentioning

confidence: 99%

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

Girmenia

Lazzarotto

Bonifazi

et al. 2019

Clinical Transplantation

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Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain

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Section: Resultsmentioning

confidence: 99%

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

Girmenia

Lazzarotto

Bonifazi

et al. 2019

Clinical Transplantation

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“…Notably, clinical isolates of human CMV differ in their tropism for HC and bone marrow stromal cells (Apperley et al, 1989;Simmons et al, 1990), so that the pathomechanism of impaired hematopoiesis likely differs between virus variants/strains. Cellular immunotherapy based on transfer of CMV-specific CD8 + T cells (Riddell et al, 1992;Walter et al, 1995;Moss and Rickinson, 2005;Feuchtinger et al, 2010;Neuenhahn et al, 2017) is an option to avoid myelosuppressive side effects as well as renal toxicity of antiviral drugs (Maffini et al, 2016) and to prevent CMV disease in those HCT recipients who are infected with drug-resistant CMV variants (Pei et al, 2017;Chemaly et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus-Associated Inhibition of Hematopoiesis Is Preventable by Cytoimmunotherapy With Antiviral CD8 T Cells

Renzaho

Podlech

Kühnapfel

et al. 2020

Front. Cell. Infect. Microbiol.

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Reactivation of latent cytomegalovirus (CMV) in recipients of hematopoietic cell transplantation (HCT) not only results in severe organ manifestations, but can also cause "graft failure" resulting in bone marrow (BM) aplasia. This inhibition of hematopoietic stem and progenitor cell engraftment is a manifestation of CMV infection that is long known in clinical hematology as "myelosuppression." Previous studies in a murine model of sex-chromosome mismatched but otherwise syngeneic HCT and infection with murine CMV have shown that transplanted hematopoietic cells (HC) initially home to the BM stroma of recipients but then fail to further divide and differentiate. Data from this model were in line with the hypothesis that infection of stromal cells, which constitute "hematopoietic niches" where hematopoiesis takes place, causes a local deficiency in essential hematopoietins. Based on this understanding, one must postulate that preventing infection of stromal cells should restore the stroma's capacity to support hematopoiesis. Adoptively-transferred antiviral CD8 + T cells prevent lethal CMV disease by controlling viral spread and histopathology in vital organs, such as liver and lungs. It remained to be tested, however, if they can also prevent infection of the BM stroma and thus allow for successful HC engraftment. Here we demonstrate that antiviral CD8 + T cells control stromal infection. By tracking male donor-derived sry + HC in the BM of infected female sry − recipients, we show the CD8 + T cells allow for successful donor HC engraftment and thereby prevent CMV-associated BM aplasia. These data provide a further argument for cytoimmunotherapy of CMV infection after HCT.

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“…The transfer of engineered virus-specific T cells has increasingly been used to treat life-threatening CMV [65], EBV [66], and ADV infections [67] after stem cell transplantation. The safety and efficacy of broad-spectrum T cells as treatment for ADV, EBV, CMV, and BKPyV infections after stem cell transplantation was published by Papadopoulou et al [68].…”

Section: Therapy With Virus-specific T Cellsmentioning

confidence: 99%

Virus-specific T cells in pediatric renal transplantation

Ahlenstiel-Grunow

Pape

2020

Pediatr Nephrol

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After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK polyomavirus (BKPyV) or Epstein-Barr virus (EBV), and less frequent from adenovirus (ADV). However, suitable predictive markers for the individual outcome of viral infections are missing and the therapeutic management remains a challenge to the success of pediatric kidney transplantation. Virus-specific T cells are known for controlling viral replication and there is growing evidence that virus-specific T cells may serve as a prognostic marker to identify patients at risk for viral complications. This review provides an overview of the usability of virus-specific T cells for improving diagnostic and therapeutic management of viral infections with reference to the necessity of antiviral prophylaxis, timing of pre-emptive therapy, and dosing of immunosuppressive medication after pediatric kidney transplantation. Several studies demonstrated that high levels of virus-specific T cells are associated with decrease of virus load and favorable outcome, whereas lack of virus-specific T cells coincided with virus-induced complications. Accordingly, the additional monitoring of virus-specific T cells aims to personalize the management of antiviral therapy, identify overimmunosuppression, and avoid unnecessary therapeutic interventions. Prospective randomized trials in pediatric kidney recipients comparing standard antiviral and immunosuppressive regimens with T cell-guided therapeutic interventions are needed, before monitoring of virus-specific T cells is implemented in the routine care of pediatric kidney graft recipients.

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Cytomegalovirus-Specific T-Cell Transfer for Refractory Cytomegalovirus Infection After Haploidentical Stem Cell Transplantation: The Quantitative and Qualitative Immune Recovery for Cytomegalovirus

Abstract: The adoptive transfer of CMV-specific T cells promotes quantitative and functional recovery of CMV-specific T cells to guard against refractory CMV infection after haplo-SCT.

Cited by 87 publications

References 35 publications

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

Cytomegalovirus-Associated Inhibition of Hematopoiesis Is Preventable by Cytoimmunotherapy With Antiviral CD8 T Cells

Virus-specific T cells in pediatric renal transplantation

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