Lymphocytes as cellular vehicles for gene therapy in mouse and man
- National Inst. of Health, Bethesda, MD (United States)
The application of bone marrow gene therapy has been stalled by the inability to achieve stable high-level gene transfer and expression in the totipotent stem cells. The authors that retroviral vectors can stably introduce genes into antigen-specific murine and human T lymphocytes in culture. Murine helper T cells were transduced with the retroviral vector SAX to express both neomycin-resistance and human adenosine deaminase genes. To determine if cultured T cells might be used for gene therapy, their persistence and continued expression of the introduced genes was evaluated in nude mice transplanted with the SAX-transduced T cells. They studied cultured human tumor-infiltrating lymphocytes as a candidate cell for a trial of gene transfer in man. Gene insertion and subsequent G418 selection did not substantially alter the growth characteristics, interleukin 2 dependence, membrane phenotype, or cytotoxicity profile of the transduced T cells. These studies provided a portion of the experimental evidence supporting the feasibility of the presently ongoing clinical trials of lymphocyte gene therapy in cancer as well as in patients with adenosine deaminase deficiency.
- OSTI ID:
- 6100079
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:8; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HEREDITARY DISEASES
THERAPY
LYMPHOCYTES
GENE RECOMBINATION
ADENOSINE
BONE MARROW CELLS
GENETIC ENGINEERING
LYASES
LYMPHOKINES
MAN
MICE
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BIOTECHNOLOGY
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DISEASES
ENZYMES
GROWTH FACTORS
LEUKOCYTES
MAMMALS
MATERIALS
MITOGENS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RIBOSIDES
RODENTS
SOMATIC CELLS
VERTEBRATES
550400* - Genetics