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Selective modification of antigen-specific T cells by RNA electroporation.

Publication ,  Journal Article
Mitchell, DA; Karikari, I; Cui, X; Xie, W; Schmittling, R; Sampson, JH
Published in: Hum Gene Ther
May 2008

It has been observed that the efficient transfection of T cells by RNA electroporation requires prior activation of T cells with mitogens or by anti-CD3 antibody stimulation. We hypothesized that this requirement for T cell activation could be leveraged to express marker genes within activated T cells responding to antigen-pulsed dendritic cells and allow for the selective enrichment and modification of antigen-specific T cells. Using electroporation of mRNA encoding green fluorescent protein as a marker gene, we demonstrate that RNA electroporation can efficiently allow for the separation of cytomegalovirus-specific CD8+ and CD4+ T cells from bulk culture responding to cytomegalovirus pp65 antigen-pulsed dendritic cells. Furthermore, we demonstrate that cytomegalovirus-specific T cells can be functionally modified by RNA transfection of the C-X-C chemokine receptor, CXCR2, to migrate efficiently toward a variety of CXCR2-specific chemokines in vitro and in vivo. These studies demonstrate the utility of RNA transfection as a simple method by which to purify and selectively modify the function of antigen-specific T cells for use in adoptive immunotherapy, and importantly provide evidence that transient expression of proteins by RNA transfection is an efficient means of modulating the in vivo function of activated T cells.

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Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

May 2008

Volume

19

Issue

5

Start / End Page

511 / 521

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Transfection
  • T-Lymphocytes
  • Receptors, Interleukin-8B
  • RNA, Messenger
  • Phosphoproteins
  • Peptides
  • Lymphocyte Activation
  • Immunotherapy, Adoptive
  • Humans
 

Citation

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Mitchell, D. A., Karikari, I., Cui, X., Xie, W., Schmittling, R., & Sampson, J. H. (2008). Selective modification of antigen-specific T cells by RNA electroporation. Hum Gene Ther, 19(5), 511–521. https://doi.org/10.1089/hum.2007.115
Mitchell, Duane A., Isaac Karikari, Xiuyu Cui, Weihua Xie, Robert Schmittling, and John H. Sampson. “Selective modification of antigen-specific T cells by RNA electroporation.Hum Gene Ther 19, no. 5 (May 2008): 511–21. https://doi.org/10.1089/hum.2007.115.
Mitchell DA, Karikari I, Cui X, Xie W, Schmittling R, Sampson JH. Selective modification of antigen-specific T cells by RNA electroporation. Hum Gene Ther. 2008 May;19(5):511–21.
Mitchell, Duane A., et al. “Selective modification of antigen-specific T cells by RNA electroporation.Hum Gene Ther, vol. 19, no. 5, May 2008, pp. 511–21. Pubmed, doi:10.1089/hum.2007.115.
Mitchell DA, Karikari I, Cui X, Xie W, Schmittling R, Sampson JH. Selective modification of antigen-specific T cells by RNA electroporation. Hum Gene Ther. 2008 May;19(5):511–521.
Journal cover image

Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

May 2008

Volume

19

Issue

5

Start / End Page

511 / 521

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Transfection
  • T-Lymphocytes
  • Receptors, Interleukin-8B
  • RNA, Messenger
  • Phosphoproteins
  • Peptides
  • Lymphocyte Activation
  • Immunotherapy, Adoptive
  • Humans