Evidence for the Cure of HIV Infection by CCR5∆32/∆32 Stem Cell Transplantation

Bodor, Josef

doi:10.15406/jhvrv.2014.01.00008

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…The PGE 2 production from iTregs can be fully suppressed by the COX inhibitor indomethacin [4]. These data indicate that PGE 2 plays an important role in differentiation of HSCs thus releasing stringency required for HLA-matching donors with potential recipients as well as with potential role in dominant suppressive effects of iTregs expressing COX-2 with acquired ability to produce copious amounts of PGE 2 responsible for delivery of suppressive function through elevated levels of cAMP [12,13].…”

Section: Prostaglandin-modulated Hematopoietic Stem Cell Transplantationmentioning

confidence: 91%

Untitled

2015

JHVRV

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Allogeneic stem cell transplantation of hematopoietic stem cells (HSCs) resistant to HIV-1 (CCR5 null cells) using a regimen to improve homing, engraftment, and preferential cord chimerism of umbilical cord blood (UCB) cells homozygous for CCR5∆32 mutation (UCBΔ32/Δ32) favors utilization of prostaglandin E 2 (PGE 2 )-mediated mechanisms to facilitate allogeneic transplantation. Since PGE 2 has additional capacity to down-regulate CCR5 expression, this could enable dual effect a) Allogeneic transplantation of UCB cells heterozygous for the CCR5∆32 mutation (UCBΔ32/wt) b) Epigenetic down-regulation of residual CCR5 expression in synergy with improved engraftment.Such treatment has capacity not only to improve engraftment of (UCBΔ32/wt) cells heterozygous for the CCR5∆32 mutation but also prevent functional expression of the CCR5 chemokine receptor used by CCR5 (R5)-tropic HIV-1 to enter CD4 + T cells. Provided that PGE 2 or its more stable analogue dimethyl-PGE 2 (dmPGE 2 ) has lasting effects in HSCs this could lead to significant increase of the number of treatable patients (frequency of heterozygous CCR5wt/∆32 donors in US and Central and North of Europe is at least 10-fold higher than in the case of homozygous CCR5∆32/∆32 donors). Thus, ultimate goal is to create a functional R5-tropic HIV-1-resistant immune system through the use of optimized dmPGE 2 -modified UCB cells heterozygous for ∆32 mutation with improved homing, engraftment, and preferential cord chimerism with further emphasis on post-transplant amelioration of the graft versus host disease (GvHD) enabled via PGE 2 -mediated potentiation of regulatory T (Treg) cell-mediated suppression.

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Section: Prostaglandin-modulated Hematopoietic Stem Cell Transplantationmentioning

confidence: 91%

Untitled

2015

JHVRV

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Hematopoietic Stem Cell-Based Therapy for HIV Disease: Prostaglandin-Modulated Transplantation

Bodor¹

2015

JHVRV

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Allogeneic stem cell transplantation of hematopoietic stem cells (HSCs) resistant to HIV-1 (CCR5 null cells) using a regimen to improve homing, engraftment, and preferential cord chimerism of umbilical cord blood (UCB) cells homozygous for CCR5∆32 mutation (UCBΔ32/Δ32) favors utilization of prostaglandin E 2 (PGE 2)-mediated mechanisms to facilitate allogeneic transplantation. Since PGE 2 has additional capacity to down-regulate CCR5 expression, this could enable dual effect a) Allogeneic transplantation of UCB cells heterozygous for the CCR5∆32 mutation (UCBΔ32/wt) b) Epigenetic down-regulation of residual CCR5 expression in synergy with improved engraftment. Such treatment has capacity not only to improve engraftment of (UCBΔ32/wt) cells heterozygous for the CCR5∆32 mutation but also prevent functional expression of the CCR5 chemokine receptor used by CCR5 (R5)-tropic HIV-1 to enter CD4 + T cells. Provided that PGE 2 or its more stable analogue dimethyl-PGE 2 (dmPGE 2) has lasting effects in HSCs this could lead to significant increase of the number of treatable patients (frequency of heterozygous CCR5wt/∆32 donors in US and Central and North of Europe is at least 10-fold higher than in the case of homozygous CCR5∆32/∆32 donors). Thus, ultimate goal is to create a functional R5-tropic HIV-1-resistant immune system through the use of optimized dmPGE 2-modified UCB cells heterozygous for ∆32 mutation with improved homing, engraftment, and preferential cord chimerism with further emphasis on post-transplant amelioration of the graft versus host disease (GvHD) enabled via PGE 2-mediated potentiation of regulatory T (Treg) cell-mediated suppression.

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Evidence for the Cure of HIV Infection by CCR5∆32/∆32 Stem Cell Transplantation

Cited by 2 publications

References 16 publications

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Hematopoietic Stem Cell-Based Therapy for HIV Disease: Prostaglandin-Modulated Transplantation

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