Immune adjuvant effect of a Toxoplasma gondii profilin-like protein in autologous whole-tumor-cell vaccination in mice.
Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR) agonist. In this study, we investigated whether TgPLP has an adjuvant effect on immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice vaccinated with AWV together with recombinant TgPLP protein had smaller CT26 tumors and increased survival. TgPLP treatment strongly increased the production of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12, and XCL1, in bone marrow-derived macrophages (BMMs). In addition, TgPLP increased the phagocytosis of tumor cells by BMMs and promoted immune cell mobility on a tumor-matrigel scaffold. TgPLP triggered immune responses as demonstrated by increased expression of antigen presenting cell markers (MHC class I and II, B7.1, and B7.2) in BMMs and increased IL-12 and IFN-γ expression in mice. Mice vaccinated with AWV and TgPLP had more immune cells (CD4+ and CD8+ T cells, natural killer cells, and macrophages) in the spleen and higher total IgG and IgG2a concentrations in the blood than mice vaccinated with AWV alone. These findings suggest that TgPLP is a TLR-based vaccine adjuvant that enhances antitumor immune responses during vaccination with AWV.
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea.|Current address: JE-UK Laboratory of Molecular Cancer Therapeutics, Yonsei Cancer Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kyoung-Ho
KH
Pyo
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea.
You-Won
YW
Lee
Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Republic of Korea.
Sun Min
SM
Lim
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea.|Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Eun-Hee
EH
Shin
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D051304:Profilins / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction; D014122:Toxoplasma / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D051304:Profilins
Toll-like receptor; Toxoplasma gondii; antitumor; profilin; vaccine
J Innate Immun. 2014;6(5):685-94
24861338
J Leukoc Biol. 2002 Feb;71(2):173-83
11818437
Nat Rev Immunol. 2014 Feb;14(2):109-21
24457485
Handb Clin Neurol. 2013;114:125-45
23829904
J Neurooncol. 2009 Jan;91(2):175-82
18797818
Ocul Immunol Inflamm. 2006 Oct;14(5):257-66
17056459
Mol Ther. 2011 Mar;19(3):594-601
21157438
Cancer Biol Ther. 2003 Nov-Dec;2(6):687-93
14688478
J Immunother. 2008 Jun;31(5):520-7
18463532
J Immunol. 1994 Sep 15;153(6):2533-43
7915739
Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(1):51-8
27181235
Curr Med Chem. 2010;17(29):3303-8
20712574
Vaccines (Basel). 2014 Apr 25;2(2):323-53
26344622
Front Oncol. 2012 Oct 09;2:132
23087898
Gene Ther. 2005 Sep;12 (17 ):1324-32
15944732
J Immunother. 2010 Oct;33(8):848-58
20842051
Br J Dermatol. 2005 May;152(5):939-47
15888150
Korean J Parasitol. 2014 Dec;52(6):605-12
25548411
Hum Vaccin Immunother. 2015;11(4):851-69
25933181
J Leukoc Biol. 2010 Jul;88(1):189-99
20360404
J Immunol. 2009 Sep 15;183(6):3634-41
19710456
Vaccine. 2013 Aug 20;31(37):3879-87
23831323
Braz J Med Biol Res. 2011 Jun;44(6):500-13
21584443
Immunol Res. 2006;36(1-3):137-46
17337774
Cytokine Growth Factor Rev. 2000 Dec;11(4):321-33
10959079
Gut. 2011 May;60(5):648-57
21199832
Clin Microbiol Rev. 2009 Apr;22(2):240-73, Table of Contents
19366914
Hum Vaccin Immunother. 2014;10(11):3261-9
25625929
Expert Rev Vaccines. 2014 Jun;13(6):721-35
24758597
J Clin Oncol. 2013 Jul 1;31(19):2413-20
23715572
Arch Virol. 2016 Aug;161(8):2075-86
27233799
Br J Cancer. 2013 May 28;108(10):1998-2004
23652314
Korean J Parasitol. 2011 Sep;49(3):303-8
22072834
Cancer Res. 2010 May 15;70(10):3945-54
20406989
Korean J Parasitol. 2010 Jun;48(2):171-4
20585536
Immunity. 2013 Jan 24;38(1):119-30
23246311
Cell Host Microbe. 2008 Feb 14;3(2):77-87
18312842
J Biol Response Mod. 1985 Dec;4(6):640-9
2418162
Hum Vaccin Immunother. 2014;10(11):3224-35
25483675
Nat Immunol. 2009 Nov;10(11):1178-84
19783988
Vaccine. 2003 Jan 30;21(7-8):787-90
12531360
Springer Semin Immunopathol. 2005 Jan;26(3):289-307
15609003
Prostate. 2009 Jun 15;69(9):917-27
19267352
Arterioscler Thromb Vasc Biol. 2015 Jan;35(1):40-9
25301842