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Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses.

Publication ,  Journal Article
Abdel-Wahab, Z; Cisco, R; Dannull, J; Ueno, T; Abdel-Wahab, O; Kalady, MF; Onaitis, MW; Tyler, DS; Pruitt, SK
Published in: J Surg Res
April 2005

BACKGROUND: Cotransfection of dendritic cells (DC) with MART-1 and constitutively active TLR4 (caTLR4) RNA enhances the maturation of DC. MATERIALS AND METHODS: Immature DC were cotransfected with RNA constructs encoding MART-1 and caTLR4, and CTL responses were analyzed. RESULTS: Cotransfection of DC with MART-1 + caTLR4 enhanced the expression of CD80 and CD83 surface markers and increased the secretion of cytokines IL-6, IL-12, and TNFalpha. Neither the native nor the A27L-modified MART-1 RNA could induce significant DC maturation or cytokine secretion. More importantly, DC cotransfected with caTLR4 + MART-1 RNA induced MART-1-specific CTL responses of a higher magnitude than DC transfected with either the native or A27L MART-1 RNA. When the MART-1 RNA-transfected DC were treated with DC-maturing cytokines, the induced CTL were less frequent and less lytic than those induced with MART-1 + caTLR4. A 2- to 100-fold increase in MART-1 tetramer+ cells and 2- to 10-fold increases in IFNgamma secretion and cytotoxicity were seen in CTL induced with MART-1 + caTLR4 compared to CTL induced with either MART-1 or A27L RNA. CTL induced with the mixed RNA displayed high percentages of CD8+ cells coexpressing CD45RA, CD56, and 2B4 antigens. Transfection with caTLR4 alone induced DC maturation, but did not induce lytic CTL, suggesting that CTL responses were induced solely by MART-1 epitopes. CONCLUSIONS: caTLR4 increases the CTL-inducing capacity of DC generating a lytic response specific for the accompanying antigen. These results demonstrate the possibility of enhancing the immunogenicity of the native MART-1 and other RNA derived from weakly immunogenic tumors in DC-based immunotherapy.

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Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

April 2005

Volume

124

Issue

2

Start / End Page

264 / 273

Location

United States

Related Subject Headings

  • Transfection
  • Toll-Like Receptors
  • Toll-Like Receptor 4
  • Surgery
  • Receptors, Cell Surface
  • RNA
  • Neoplasm Proteins
  • Membrane Glycoproteins
  • MART-1 Antigen
  • Interferon-gamma
 

Citation

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Chicago
ICMJE
MLA
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Abdel-Wahab, Z., Cisco, R., Dannull, J., Ueno, T., Abdel-Wahab, O., Kalady, M. F., … Pruitt, S. K. (2005). Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses. J Surg Res, 124(2), 264–273. https://doi.org/10.1016/j.jss.2004.10.002
Abdel-Wahab, Zeinab, Robin Cisco, Jens Dannull, Tomio Ueno, Omar Abdel-Wahab, Matthew F. Kalady, Mark W. Onaitis, Douglas S. Tyler, and Scott K. Pruitt. “Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses.J Surg Res 124, no. 2 (April 2005): 264–73. https://doi.org/10.1016/j.jss.2004.10.002.
Abdel-Wahab Z, Cisco R, Dannull J, Ueno T, Abdel-Wahab O, Kalady MF, et al. Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses. J Surg Res. 2005 Apr;124(2):264–73.
Abdel-Wahab, Zeinab, et al. “Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses.J Surg Res, vol. 124, no. 2, Apr. 2005, pp. 264–73. Pubmed, doi:10.1016/j.jss.2004.10.002.
Abdel-Wahab Z, Cisco R, Dannull J, Ueno T, Abdel-Wahab O, Kalady MF, Onaitis MW, Tyler DS, Pruitt SK. Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses. J Surg Res. 2005 Apr;124(2):264–273.
Journal cover image

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

April 2005

Volume

124

Issue

2

Start / End Page

264 / 273

Location

United States

Related Subject Headings

  • Transfection
  • Toll-Like Receptors
  • Toll-Like Receptor 4
  • Surgery
  • Receptors, Cell Surface
  • RNA
  • Neoplasm Proteins
  • Membrane Glycoproteins
  • MART-1 Antigen
  • Interferon-gamma