Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA.
Stabilized synthetic RNA oligonucleotides (ORN) and protected messenger RNA (mRNA) were recently discovered to possess an immunostimulatory capacity through their recognition by TLR 7 and 8. We wanted to find out whether this danger signal is capable of triggering anti-tumor immunity when injected locally into an established tumor. Using the mouse glioma tumor cell line SMA-560 in syngenic VM/Dk mice, we were able to show that intra-tumor injections of protamine-stabilized mRNA do indeed induce tumor regression and long-term anti-tumor immunity. Residual RNA-injected tumors show CD8 infiltration. Distant injections of protamine-protected mRNA and intra-tumor injection of naked mRNA also result in anti-tumor immunity. Although they are strong danger signals, RNA are labile molecules with a short half-life: they do not trigger side effects such as long-term, uncontrolled immunostimulation evidenced by splenomegaly in CpG DNA-treated mice. In conclusion, RNA molecules are potent and safe danger signals that are relevant for active immunotherapy strategies aimed at the eradication of solid tumors.
Scheel
Birgit
B
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
Aulwurm
Steffen
S
Probst
Jochen
J
Stitz
Lothar
L
Hoerr
Ingmar
I
Rammensee
Hans-Georg
HG
Weller
Michael
M
Pascolo
Steve
S
D000818:Animals; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000276:immunology; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology*; D011479:Protamines / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology* / Q000627:therapeutic use*
D011479:Protamines; D012333:RNA, Messenger; D004247:DNA