Viral-specific adoptive immunotherapy after allo-SCT: the role of multimer-based selection strategies

Ramírez, Natalia; Olavarría, Eduardo

doi:10.1038/bmt.2012.262

Cited by 15 publications

(5 citation statements)

References 51 publications

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“…The effect of an impaired immune response can be observed in immunocompromised patients that can result in several CMV pathologies and mortality [71]. Adoptive transfer of HCMV-specific T cells has been considered a proven strategy to prevent HCMV disease following bone marrow transplantation [72,73,74,75]. However, following HCMV infection, aggravated HCMV specific cell mediated immunity could progressively alter the composition of the T cell repertoire by inducing a decrease of naïve T cells and an increase of highly differentiated T cells.…”

Section: Host Responses To Hcmv Infectionmentioning

confidence: 99%

Battle between Host Immune Cellular Responses and HCMV Immune Evasion

Manandhar

Hò

Pump

et al. 2019

IJMS

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Human cytomegalovirus (HCMV) is ubiquitously prevalent. HCMV infection is typically asymptomatic and controlled by the immune system in healthy individuals, yet HCMV can be severely pathogenic for the fetus during pregnancy and in immunocompromised persons, such as transplant recipients or HIV infected patients. HCMV has co-evolved with the hosts, developed strategies to hide from immune effector cells and to successfully survive in the human organism. One strategy for evading or delaying the immune response is maintenance of the viral genome to establish the phase of latency. Furthermore, HCMV immune evasion involves the downregulation of human leukocyte antigens (HLA)-Ia molecules to hide infected cells from T-cell recognition. HCMV expresses several proteins that are described for downregulation of the HLA class I pathway via various mechanisms. Here, we review the wide range of immune evasion mechanisms of HCMV. Understanding the mechanisms of HCMV immune evasion will contribute to the development of new customized therapeutic strategies against the virus.

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Section: Host Responses To Hcmv Infectionmentioning

confidence: 99%

Battle between Host Immune Cellular Responses and HCMV Immune Evasion

Manandhar

Hò

Pump

et al. 2019

IJMS

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“…This approach has been recently reviewed and advocated (73), but some limitations, intrinsic in the multimer strategy, should be considered. Multimer selection for immune reconstitution is limited to CD8 CTL and restricted to the HLA alleles available at present for multimer construction.…”

Section: Discussionmentioning

confidence: 99%

Preservation of Antigen-Specific Functions of αβ T Cells and B Cells Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy

et al. 2017

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Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.

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“…Unfortunately, response to cell therapy appears to be limited to patients with less clinically advanced PTLD, with durable PTLD control being related to early in-vivo expansion similar to DLI ( 117 ). The selection technique through virus peptide bound to HLA class I multimers has been developed also for the selection of EBV specific CD8+ lymphocytes, but clinical data are still awaited ( 118 ).…”

Section: Management Of Viral Infections After Hsctmentioning

confidence: 99%

Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications

et al. 2021

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In spite of an increasing array of investigations, the relationships between viral infections and allogeneic hematopoietic stem cell transplantation (HSCT) are still controversial, and almost exclusively regard DNA viruses. Viral infections per se account for a considerable risk of morbidity and mortality among HSCT recipients, and available antiviral agents have proven to be of limited effectiveness. Therefore, an optimal management of viral infection represents a key point in HSCT strategies. On the other hand, viruses bear the potential of shaping immunologic recovery after HSCT, possibly interfering with control of the underlying disease and graft-versus-host disease (GvHD), and eventually with HSCT outcome. Moreover, preliminary data are available about the possible role of some virome components as markers of immunologic recovery after HSCT. Lastly, HSCT may exert an immunotherapeutic effect against some viral infections, notably HIV and HTLV-1, and has been considered as an eradicating approach in these indications.

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Viral-specific adoptive immunotherapy after allo-SCT: the role of multimer-based selection strategies

Cited by 15 publications

References 51 publications

Battle between Host Immune Cellular Responses and HCMV Immune Evasion

Battle between Host Immune Cellular Responses and HCMV Immune Evasion

Preservation of Antigen-Specific Functions of αβ T Cells and B Cells Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy

Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications

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