An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model.
BACKGROUND
Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22-24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy.


METHODS
In this study, the experiments were designed including prevention and therapeutic stages in order to attain effect against tumor recurrence in clinical settings. The anti-tumor efficacy of a novel cytokine adjuvant vaccine that contained cytokines GM-CSF and IL-2 and inactivated colon CT26.WT whole cell antigen was evaluated in BALB/c mouse tumor models by measuring tumor growth post vaccination and the survival time of tumor-bearing mice, analyzing the expression and distribution of CD4, CD8, CD11c, CD80, CD86 and CD83 positive cells in control and treated mice by flow cytometry and immunochemistry. The tumor-specific cytotoxic T cells (CTL) were analyzed by tumor proliferation and the lactic dehydrogenates (LDH) release assays. IFN-γ, IL-2 and GM-CSF secretion in serum was assayed by ELISA.


RESULTS
Our results suggested that cytokine adjuvant vaccine significantly inhibited tumor growth and extended the survival period at least 160d. It was found that the levels of CD8 + T and the tumor-specific cytotoxicity were significantly higher in prevention and treatment group vaccinated by cytokine adjuvant vaccine. CD8 + T cells play a key role in anti-tumor response.


CONCLUSIONS
The novel GM-CSF and IL-2 based adjuvant vaccine effectively activated autologous T-cell response and represented a promising immunotherapeutic approach for patients with colon cancer.
Department of Immunology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.|Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, 150081, China.
Huanyu
H
Ju
Department of Immunology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.|Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, 150081, China.
Wenjing
W
Xing
Department of Immunology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.|Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, 150081, China.
Jinfeng
J
Yang
Department of Immunology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.|Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, 150081, China.
Yang
Y
Zheng
Department of Immunology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.|Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, 150081, China.
Xiuzhi
X
Jia
Department of Immunology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.|Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, 150081, China.
Benning
B
Zhang
Department of Immunology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China. huanren2009@126.com.|Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, 150081, China. huanren2009@126.com.
Huan
H
Ren
CT26.WT; Colon cancer; Cytokine adjuvant; Immunotherapy; Tumor vaccine
J Clin Oncol. 2009 Dec 10;27(35):5911-8
19805669
Nat Immunol. 2015 Jun;16(6):609-17
25915731
Cancer Res. 2003 Oct 1;63(19):6378-86
14559827
Cancer. 2000 Dec 15;89(12):2637-45
11135226
Expert Rev Vaccines. 2005 Jun;4(3):259-74
16026242
Ann Surg Oncol. 2014 Nov;21(12):3931-7
24943235
Cancer Immunol Immunother. 2015 Apr;64(4):459-65
25603775
Ann Surg Oncol. 2003 Aug;10(7):810-20
12900373
World J Gastroenterol. 2015 Apr 21;21(15):4491-8
25914457
Laeknabladid. 2014 Feb;100(2):75-82
24639430
Cancer Treat Rev. 2016 Jan;42:82-90
26608114
J Immunol. 2014 Jun 15;192(12):5451-8
24907378
Clin Cancer Res. 2008 Mar 1;14(5):1455-63
18316569
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3539-43
8097319
Immunotherapy. 2012 Jun;4(6):577-80
22788125
J Immunol Res. 2014;2014:897214
24741629
Clin Transl Sci. 2008 Dec;1(3):228-39
20357913
Ann Surg. 2011 Feb;253(2):328-35
21217520
Cell Cycle. 2006 Feb;5(3):246-9
16418579
Hum Gene Ther. 1999 Aug 10;10(12):1983-91
10466632
Iran J Cancer Prev. 2015 Aug;8(4):e3439
26478796
Cancer Immunol Immunother. 2002 Apr;51(2):63-71
11904730
Exp Hematol Oncol. 2014 Jan 23;3(1):3
24456704
Biochem Biophys Res Commun. 2005 Jul 22;333(1):223-9
15958210
Health Technol Assess. 2013 Apr;17(14):1-237
23547747
World J Gastroenterol. 2013 Dec 14;19(46):8531-42
24379570
J Cancer Res Clin Oncol. 2011 Feb;137(2):305-10
20407789
Cancer Immunol Immunother. 2016 Apr;65(4):383-92
26894495