Pretransplant mobilization with granulocyte colony-stimulating factor improves B-cell reconstitution by lentiviral vector gene therapy in SCID-X1 mice.

[severe combined immunodeficiency]

Hematopoietic stem cell (HSC ) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID -X 1 ), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients . Cytoreductive preconditioning is known to improve HSC engraftment , but in general it is not considered for SCID -X 1 since the poor health of most of these patients at diagnosis and the risk of toxicity preclude the conditioning used in standard bone marrow stem cell transplantation . We hypothesized that mobilization of HSC by granulocyte colony-stimulating factor (G-CSF ) should create temporary space in bone marrow niches to improve engraftment and thereby B-cell reconstitution . In the present pilot study supplementing our earlier preclinical evaluation (Huston et al ., 2011 ), Il 2 rg (-/-) mice pretreated with G-CSF were transplanted with wild-type lineage negative (Lin (-)) cells or Il 2 rg (-/-) Lin (-) cells transduced with therapeutic IL 2 RG lentiviral vectors . Mice were monitored for reconstitution of lymphocyte populations , level of donor cell chimerism , and antibody responses as compared to 2 â€‰Gy total body irradiation (TBI ), previously found effective in promoting B-cell reconstitution . The results demonstrate that G-CSF promotes B-cell reconstitution similar to low -dose TBI and provides proof of principle for an alternative approach to improve efficacy of gene therapy in SCID patients without adverse effects associated with cytoreductive conditioning .

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Diseases presenting "been deficient in many of the gene therapy" symptom

severe combined immunodeficiency

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