T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients

Stanley R. Riddell, Mark Elliott, Deborah Lewinsohn, Mark J. Gilbert, Linda Wilson, Sara A. Manley, Stephen D. Lupton, Robert W. Overell, Thomas C. Reynolds, Lawrence Corey, Philip D. Greenberg

Research output: Contribution to journalArticle

470 Citations (Scopus)

Abstract

The introduction and expression of genes in somatic cells is an innovative therapy for correcting genetic deficiency diseases and augmenting immune function. A potential obstacle to gene therapy is the elimination of such gene-modified cells by an immune response to novel protein products of the introduced genes. We are conducting an immunotherapy trial in which individuals seropositive for human immunodeficiency virus (HIV) receive CD8+ HIV-specific cytotoxic T cells modified by retroviral transduction to express a gene permitting positive and negative selection. However, five of six subjects developed cytotoxic T-lymphocyte responses specific for the novel protein and eliminated the transduced cytotoxic T cells. The rejection of genetically modified cells by these immunocompromised hosts suggests that strategies to render gene-modified cells less susceptible to host immune surveillance will be required for successful gene therapy of immunocompetent hosts.

Original languageEnglish (US)
Pages (from-to)216-223
Number of pages8
JournalNature Medicine
Volume2
Issue number2
DOIs
StatePublished - 1996
Externally publishedYes

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T-cells
Cytotoxic T-Lymphocytes
Viruses
Genes
HIV
T-Lymphocytes
Gene therapy
Genetic Therapy
Deficiency Diseases
Investigational Therapies
Inborn Genetic Diseases
Immunocompromised Host
Immunotherapy
Proteins
Gene Expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Riddell, S. R., Elliott, M., Lewinsohn, D., Gilbert, M. J., Wilson, L., Manley, S. A., ... Greenberg, P. D. (1996). T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nature Medicine, 2(2), 216-223. https://doi.org/10.1038/nm0296-216

T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. / Riddell, Stanley R.; Elliott, Mark; Lewinsohn, Deborah; Gilbert, Mark J.; Wilson, Linda; Manley, Sara A.; Lupton, Stephen D.; Overell, Robert W.; Reynolds, Thomas C.; Corey, Lawrence; Greenberg, Philip D.

In: Nature Medicine, Vol. 2, No. 2, 1996, p. 216-223.

Research output: Contribution to journalArticle

Riddell, SR, Elliott, M, Lewinsohn, D, Gilbert, MJ, Wilson, L, Manley, SA, Lupton, SD, Overell, RW, Reynolds, TC, Corey, L & Greenberg, PD 1996, 'T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients', Nature Medicine, vol. 2, no. 2, pp. 216-223. https://doi.org/10.1038/nm0296-216
Riddell, Stanley R. ; Elliott, Mark ; Lewinsohn, Deborah ; Gilbert, Mark J. ; Wilson, Linda ; Manley, Sara A. ; Lupton, Stephen D. ; Overell, Robert W. ; Reynolds, Thomas C. ; Corey, Lawrence ; Greenberg, Philip D. / T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. In: Nature Medicine. 1996 ; Vol. 2, No. 2. pp. 216-223.
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