Promoting effect of Antrodia camphorata as an immunomodulating adjuvant on the antitumor efficacy of HER-2/neu DNA vaccine.
It is well known that DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. Antrodia camphorata (AC) is a unique basidiomycete fungus of the Polyporaceae family that only grows on the aromatic tree Cinnamomum kanehirai Hayata (Lauraceae) endemic to Taiwan. Importantly, AC has been shown to be highly beneficial in the treatment and prevention of cancer. The goal of this study was to investigate whether AC is able to augment the antitumor immune properties of a HER-2/neu DNA vaccine in a mouse model in which p185neu is overexpressed in MBT-2 tumor cells. Compared with the mice that received the HER-2/neu DNA vaccine alone, co-treatment with AC suppressed tumor growth and extended the survival rate. This increase in the antitumor efficacy was attributed to the enhancement of the Th1-like cellular immune response by the HER-2/neu DNA vaccine-AC combination. Evidence for this came from the marked increase in the IFN-gamma mRNA expression in CD4+ T cells in the draining inguinal lymph nodes, an increase in the number of functional HER-2/neu-specific CTLs, and the increased tumor infiltration of both CD4+ and CD8+ T cells, depletion of which abolishes the antitumor effect of the HER-2/neu DNA vaccine-AC therapy. Our results further indicate that the treatment of mice with AC enhanced DC activation and production of Th1-activating cytokines (e.g. IL-12, and IFN-alpha) in the draining lymph nodes, which were sufficient to directly stimulate T cell proliferation and higher IFN-gamma production in response to ErbB2. Overall, these results clearly demonstrate that AC represents a promising immunomodulatory adjuvant that could enhance the therapeutic potency of HER-2/neu DNA vaccines in cancer therapy.
Huang
Chia-Hsin
CH
Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan, ROC.
Chang
Chia-Che
CC
Lin
Chiu-Mei
CM
Wang
Sin-Ting
ST
Wu
Min-Tze
MT
Li
Eric I C
EI
Chang
Hsien-Chang
HC
Lin
Chi-Chen
CC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D055491:Antrodia; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D002457:Cell Extracts / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D019444:Vaccines, DNA
D000276:Adjuvants, Immunologic; D002457:Cell Extracts; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C524056:Erbb2 protein, mouse
Int Heart J. 2009 Mar;50(2):207-20
19367031
Planta Med. 2004 Apr;70(4):310-4
15095145
Life Sci. 2003 Oct 10;73(21):2769-83
13679244
Mol Ther. 2007 Feb;15(2):404-10
17235320
Mol Ther. 2004 Aug;10(2):290-301
15294176
Science. 1989 May 12;244(4905):707-12
2470152
Cancer Res. 2005 Apr 15;65(8):3437-46
15833879
FEMS Microbiol Lett. 2002 Mar 19;209(1):63-7
12007655
Semin Immunol. 1997 Oct;9(5):271-83
9327522
Toxicol Appl Pharmacol. 2008 Mar 1;227(2):291-8
18078970
Cancer Res. 2000 Feb 15;60(4):1035-42
10706121
Cancer Immunol Immunother. 2009 May;58(5):737-48
18815785
Hum Gene Ther. 1996 Nov 10;7(17):2185-94
8934232
Food Chem Toxicol. 2007 Jul;45(7):1249-57
17316946
Hum Gene Ther. 2007 Nov;18(11):1129-39
17939748
J Ethnopharmacol. 2008 Nov 20;120(2):196-203
18778764
J Exp Med. 2002 Aug 19;196(4):541-9
12186845
Clin Cancer Res. 2008 May 15;14(10):3185-92
18483387
J Nat Prod. 2004 Jan;67(1):46-8
14738384
J Virol. 1996 Dec;70(12):9074-8
8971047
Toxicol Appl Pharmacol. 2004 Dec 1;201(2):186-93
15541758
Expert Opin Biol Ther. 2004 Jun;4(6):889-900
15174971
Cancer. 2001 Oct 1;92(7):1896-904
11745263
Cancer Treat Res. 2005;123:137-56
16211869
J Agric Food Chem. 2003 May 21;51(11):3302-8
12744658
Clin Cancer Res. 2007 Oct 15;13(20):6195-203
17947487
J Gene Med. 2008 Jun;10(6):679-89
18324638
Nutr Cancer. 2007;57(1):111-21
17516868
Clin Cancer Res. 2005 Mar 1;11(5):1941-52
15756020
Genet Vaccines Ther. 2009 Jan 30;7:2
19178753
Vaccine. 2007 Jan 8;25(4):719-28
16962215
J Immunol. 2003 Mar 15;170(6):3162-70
12626574
Life Sci. 2002 Jun 14;71(4):469-82
12044846
Proteomics. 2006 Feb;6(3):826-35
16411266
Nat Med. 1996 Oct;2(10):1122-8
8837611
Adv Immunol. 2006;90:175-213
16730264
Semin Cancer Biol. 2002 Feb;12(1):33-42
11926410
J Agric Food Chem. 2002 May 22;50(11):3322-7
12010005
J Agric Food Chem. 2005 Jul 13;53(14):5559-64
15998114
Biosci Biotechnol Biochem. 2007 Jan;71(1):23-30
17213674
J Ethnopharmacol. 2007 Jan 3;109(1):93-103
16930895
Arch Toxicol. 2009 Feb;83(2):121-9
18709356
Nature. 1986 Jan 16-22;319(6050):226-30
3945311
Mol Ther. 2008 Dec;16(12):2011-21
18813280
Anticancer Res. 1998 May-Jun;18(3A):1585-9
9673374
Cancer Res. 1995 Jun 1;55(11):2422-30
7757996
Cancer Res. 2004 Apr 15;64(8):2858-64
15087404