Anti-tumor activity of dendritic cells transfected with mRNA for receptor for hyaluronan-mediated motility is mediated by CD4+ T cells.
Receptor for hyaluronan-mediated motility ( RHAMM) is overexpressed in various tumors with high frequency, and was recently identified as an immunogenic antigen by serologic screening of cDNA expression libraries. In this study, we explored whether RHAMM is a potential target for dendritic cell (DC) immunotherapy. We constructed a plasmid for transduction of in vitro-transcribed mRNAs into DCs to efficiently transport the intracellular protein RHAMM into MHC class II compartments by adding a late endosomal/lysosomal sorting signal to the RHAMM gene. Immunization of mice with modified RHAMM mRNA-transfected DCs (DC/ RHAMM) induced killing activity against RHAMM-positive tumor cells in splenocytes. To examine whether CD4(+) and/or CD8(+) T cells were required for this antitumor immunity, an anti-CD4 or anti-CD8 antibody was administered to mice after immunization with DC/ RHAMM. Depletion of CD4(+) T cells significantly diminished the induction of tumor cell-killing activity in splenocytes, whereas CD8(+) T cell depletion had no effect. We then investigated the therapeutic effect of DC/ RHAMM in a 3-day tumor model of EL4. DC/ RHAMM was administered to mice on days 3, 7 and 10 after EL4 tumor inoculation. The treatment markedly inhibited tumor growth compared to control DCs. Moreover, antibody-mediated depletion of CD4(+) T cells completely abrogated the therapeutic effect of DC/ RHAMM, whereas depletion of CD8(+) T cells had no effect. The results of this preclinical study indicate that DCs transfected with a modified RHAMM mRNA targeted to MHC class II compartments can induce CD4(+) T cell-mediated antitumor activity in vivo.[1]References
- Anti-tumor activity of dendritic cells transfected with mRNA for receptor for hyaluronan-mediated motility is mediated by CD4+ T cells. Fukui, M., Ueno, K., Suehiro, Y., Hamanaka, Y., Imai, K., Hinoda, Y. Cancer Immunol. Immunother. (2006) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
