DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor.
The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8(+) T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK- and CD8(+) T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.
Zhou
He
H
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Luo
Yunping
Y
Lo
Jeng-fan
JF
Kaplan
Charles D
CD
Mizutani
Masato
M
Mizutani
Noriko
N
Lee
Jiing-Dwan
JD
Primus
F James
FJ
Becker
Jürgen C
JC
Xiang
Rong
R
Reisfeld
Ralph A
RA
D000222:Adaptation, Physiological; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D051034:Inhibitor of Apoptosis Proteins; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D012097:Repressor Proteins; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology*
C117749:Birc5 protein, mouse; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015789:HLA-A2 Antigen; D051034:Inhibitor of Apoptosis Proteins; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D012097:Repressor Proteins; D000077022:Survivin; D019444:Vaccines, DNA; C114735:minor H antigen H60