Cancer immunotherapy using RNA-loaded dendritic cells - PubMed (original) (raw)

Review

Cancer immunotherapy using RNA-loaded dendritic cells

P Ponsaerts et al. Clin Exp Immunol. 2003 Dec.

Abstract

Dendritic cells (DC) are the most professional antigen-presenting cells of the immune system and are capable of initiating immune responses in vitro and in vivo. One of the great challenges in immunotherapy protocols is to introduce relevant antigens into DC for stimulation of major histocompatibility complex (MHC) class I- and class II-restricted anti-tumour or anti-viral immunity. This review will focus on the development of mRNA-loaded DC-based immunotherapy vaccines. First, several published results concerning mRNA transfection efficiency in DC are compared. Next, an overview is given for several published studies describing CD8+ and CD4+ T-cell clone activation using RNA-loaded DC. These data show that RNA-loaded DC efficiently process and present antigenic epitopes. Next, published data from in vitro T-cell activation studies using RNA-loaded DC are summarized and provide evidence that RNA-loaded DC can efficiently stimulate in vitro primary and secondary immune responses. Finally, the summarized data provide evidence that RNA-loaded DC are a promising strategy for the development of future cancer vaccination strategies.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Proposed model for the induction of immunity by type I dendritic cells (DC1).

Fig. 2

Fig. 2

Comparison of EGFP mRNA electroporation and DNA electroporation in K562 cells. K562 cells were electroporated at 300 V and 150 _µ_F in a 4-mm standard electroporation cuvette with 20 _µ_g EGFP mRNA or 20 _µ_g EGFP DNA. In a time-course, the percentage of EGFP-positive cells was followed flowcytometrically by percentage (left side), as well as mean fluorescence intensity (MFI) of EGFP positive cells (right side).

Fig. 3

Fig. 3

Antigen presentation by MAGE-A1 mRNA-electroporated dendritic cells. HLA-A1-positive immature Mo-DC were cultured with GM-CSF and IL-4 and transfected at day 6 of culture by electroporation with MAGE-A1 mRNA or with EGFP mRNA. HLA-A1-positive Mo-DC pulsed with a MAGE-A1 peptide, and HLA-A1-negative Mo-DC electroporated with MAGE-A1 mRNA or pulsed with MAGE-A1 peptide served as controls. Antigen-presenting cells (indicated on the left of the graph) were co-incubated with a HLA-A1-restricted MAGE-A1 specific CD8+ CTL clone to determine antigen loading eficiency, as reflected by IFN-γ production of the CTL clone. Results are shown as mean ± s.d.

Similar articles

Cited by

References

    1. Van Tendeloo VFI, Van Broeckhoven C, Berneman ZN. Gene-based cancer vaccines: an ex vivo approach. Leukemia. 2001;15:545–58. - PubMed
    1. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52. - PubMed
    1. Dhodapkar MV, Steinman RM. Antigen-bearing immature dendritic cells induce peptide-specific CD8 (+) regulatory T cells in vivo in humans. Blood. 2002;100:174–7. - PubMed
    1. Jonuleit H, Schmitt E, Kakirman H, Stassen M, Knop J, Enk AH. Infectious tolerance: human CD25 (+) regulatory T cells convey suppressor activity to conventional CD4 (+) T helper cells. J Exp Med. 2002;196:255–60. - PMC - PubMed
    1. Czerniecki BJ, Cohen PA, Faries M, Xu S, Roros JG, Bedrosian I. Diverse functional activity of CD83+ monocyte-derived dendritic cells and implications for cancer vaccines. Crit Rev Immunol. 2001;21:157–78. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources