Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and in CD34+ stem cell–engrafted NOD/SCID/IL-2Rγcnull mice

Thomas, Simone; Klobuch, Sebastian; Sommer, Maria; Ewijk, Reyn van; Theobald, Matthias; Meyer, Ralf G.; Herr, Wolfgang

doi:10.1016/j.exphem.2013.09.013

Cited by 6 publications

(5 citation statements)

References 48 publications

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“…Our study has demonstrated that 2x10 5 CD34 + cells was the optimal cell dose that will achieve high engraftment level with high consistency. The average percentage of hCD45 + cells in peripheral blood was 16.5%, which was similar to previous studies (165,181,201), however other studies that had a much higher percentage of hCD45 + cells after engraftment (169,192). This variation could be due to the difference in the purity of CD34 + cells.…”

Section: Discussionsupporting

confidence: 88%

Development of humanised mouse model for DC based immunotherapy

Minoda¹

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Dendritic cells (DCs) are professional antigen presenting cells (APC) that orchestrate the immune response. These cells play a major role in inducing primary immune response by activating naïve CD8 + and CD4 + T cells. In mice, CD8 + DC is the major DC subset that excels in priming CD8 + T cells to become cytotoxic T cells (CTL), critical to induce anti-tumour and anti-viral immunity. Human peripheral blood, lymphoid and nonlymphoid organs contain 3 major DC subsets, plasmacytoid dendritic cells (pDCs), CD1c + and CD141 + myeloid DCs, each with distinct functional characteristics. Comparative transcriptome analysis enabled close alignment of human

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Section: Discussionsupporting

confidence: 88%

Development of humanised mouse model for DC based immunotherapy

Minoda¹

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“…Another option for adaptation of the model to clinical needs could be the transfer of defined T-cell subsets with stem cell properties [ 101 ]. Finally, and most obviously, NSG/HHD adoptive transfer recipients could be further ‘humanized’ by human CD34 + stem-cell transplantation to reconstitute them with human immune system for the priming of intrinsic antiviral effector and helper cells [ 102 , 103 ] that take over for enduring viral control after the transient protection by adoptive immunotherapy has prevented life-threatening early-onset CMV disease.…”

Section: Discussionmentioning

confidence: 99%

Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice

et al. 2015

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Reactivation of human cytomegalovirus (HCMV) can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease.

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“…On the other hand, allogeneic T cells might serve as a platform for EBV + tumor specific receptor expression, but these allogeneic T cells bear the danger of eliciting graft-versus-host-disease (GvHD). However, it was noted that EBV specific T cells carry only low alloreactivity [90], and are therefore favored as an allogeneic source in several clinical trials (Table 1). Along these lines, allogeneic EBV specific T cells could be banked and transduced with either HLA matched EBV specific TCRs, or tumor specific CARs, for infusion into patients with EBV associated malignancies.…”

Section: Clinical Development Of Ebv Specific Tcrs and B Cell Specifimentioning

confidence: 99%

Redirecting T Cells against Epstein–Barr Virus Infection and Associated Oncogenesis

Münz¹

2020

Cells

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The Epstein–Barr virus (EBV) is associated with lymphomas and carcinomas. For some of these, the adoptive transfer of EBV specific T cells has been therapeutically explored, with clinical success. In order to avoid naturally occurring EBV specific autologous T cell selection from every patient, the transgenic expression of latent and early lytic viral antigen specific T cell receptors (TCRs) to redirect T cells, to target the respective tumors, is being developed. Recent evidence suggests that not only TCRs against transforming latent EBV antigens, but also against early lytic viral gene products, might be protective for the control of EBV infection and associated oncogenesis. At the same time, these approaches might be more selective and cause less collateral damage than targeting general B cell markers with chimeric antigen receptors (CARs). Thus, EBV specific TCR transgenic T cells constitute a promising therapeutic strategy against EBV associated malignancies.

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Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and in CD34+ stem cell–engrafted NOD/SCID/IL-2Rγcnull mice

Cited by 6 publications

References 48 publications

Development of humanised mouse model for DC based immunotherapy

Development of humanised mouse model for DC based immunotherapy

Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice

Redirecting T Cells against Epstein–Barr Virus Infection and Associated Oncogenesis

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