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Mol Ther. 2003 Dec;8(6):981-91.

Induction of transgene-specific immunological tolerance in myeloablated nonhuman primates using lentivirally transduced CD34+ progenitor cells.

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1
Department of Microbiology, Immunology & Molecular Genetics, and Medicine, UCLA AIDS Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.

Abstract

Modeling human hematopoietic progenitor cell gene therapy in nonhuman primates allows long-term evaluation of safety, maintenance of gene expression, and potential immune response against transgene products. We transplanted autologous G-CSF/SCF-mobilized CD34+ cells transduced with lentiviral vectors expressing EGFP into myeloablated rhesus macaques. To date, more than 4 years posttransplantation, 0.5-8% EGFP expression is maintained in multiple cell lineages. The animals remain healthy with no evidence of hematopoietic abnormalities or malignancies. To assess immune functions, we actively immunized two of our transplanted animals with purified rEGFP proteins and CpG adjuvant and demonstrated stable levels of EGFP+ cell populations maintained for over 29 months despite four active immunizations. We did not detect a persistent anti-EGFP antibody response or anti-EGFP T cell response in these immunized animals. Immune response to an irrelevant antigen was normal. Taken together, our data provide formal support that transplantation of lentivirally transduced CD34+ progenitor cells in myeloablated rhesus macaques induces specific immunological tolerance toward a foreign transgene.

PMID:
14664801
[Indexed for MEDLINE]
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