In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys

Kenneth W. Culver, Richard A. Morgan, William R A Osborne, Robert T. Lee, Deborah Lenschow, Cynthia Able, Kenneth Cornetta, W. French Anderson, R. Michael Blaese

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genes in vitro for long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes both in vitro and in vivo to determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (HADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periods in vivo and can continue to express the introduced genes.

Original languageEnglish (US)
Pages (from-to)399-410
Number of pages12
JournalHuman Gene Therapy
Volume1
Issue number4
StatePublished - 1990
Externally publishedYes

Fingerprint

Macaca mulatta
T-Lymphocytes
Gene Expression
Neomycin
Genes
Lymphocytes
DNA-Directed DNA Polymerase
Genetic Therapy
Primates
Lymph Nodes
Polymerase Chain Reaction
Growth

ASJC Scopus subject areas

  • Genetics

Cite this

Culver, K. W., Morgan, R. A., Osborne, W. R. A., Lee, R. T., Lenschow, D., Able, C., ... Blaese, R. M. (1990). In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys. Human Gene Therapy, 1(4), 399-410.

In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys. / Culver, Kenneth W.; Morgan, Richard A.; Osborne, William R A; Lee, Robert T.; Lenschow, Deborah; Able, Cynthia; Cornetta, Kenneth; Anderson, W. French; Blaese, R. Michael.

In: Human Gene Therapy, Vol. 1, No. 4, 1990, p. 399-410.

Research output: Contribution to journalArticle

Culver, KW, Morgan, RA, Osborne, WRA, Lee, RT, Lenschow, D, Able, C, Cornetta, K, Anderson, WF & Blaese, RM 1990, 'In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys', Human Gene Therapy, vol. 1, no. 4, pp. 399-410.
Culver KW, Morgan RA, Osborne WRA, Lee RT, Lenschow D, Able C et al. In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys. Human Gene Therapy. 1990;1(4):399-410.
Culver, Kenneth W. ; Morgan, Richard A. ; Osborne, William R A ; Lee, Robert T. ; Lenschow, Deborah ; Able, Cynthia ; Cornetta, Kenneth ; Anderson, W. French ; Blaese, R. Michael. / In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys. In: Human Gene Therapy. 1990 ; Vol. 1, No. 4. pp. 399-410.
@article{fd91f42eecac4fc18045b49862447b68,
title = "In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys",
abstract = "Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genes in vitro for long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes both in vitro and in vivo to determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (HADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periods in vivo and can continue to express the introduced genes.",
author = "Culver, {Kenneth W.} and Morgan, {Richard A.} and Osborne, {William R A} and Lee, {Robert T.} and Deborah Lenschow and Cynthia Able and Kenneth Cornetta and Anderson, {W. French} and Blaese, {R. Michael}",
year = "1990",
language = "English (US)",
volume = "1",
pages = "399--410",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys

AU - Culver, Kenneth W.

AU - Morgan, Richard A.

AU - Osborne, William R A

AU - Lee, Robert T.

AU - Lenschow, Deborah

AU - Able, Cynthia

AU - Cornetta, Kenneth

AU - Anderson, W. French

AU - Blaese, R. Michael

PY - 1990

Y1 - 1990

N2 - Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genes in vitro for long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes both in vitro and in vivo to determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (HADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periods in vivo and can continue to express the introduced genes.

AB - Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genes in vitro for long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes both in vitro and in vivo to determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (HADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periods in vivo and can continue to express the introduced genes.

UR - http://www.scopus.com/inward/record.url?scp=0025655886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025655886&partnerID=8YFLogxK

M3 - Article

C2 - 1964096

AN - SCOPUS:0025655886

VL - 1

SP - 399

EP - 410

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 4

ER -