An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model.

Huanyu Ju,Xiuzhi Jia,Jinfeng Yang,Benning Zhang,Wenjing Xing,Yang Zheng,Huan Ren

doi:10.1186/s12865-016-0172-x

Abstract

BackgroundDespite 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.MethodsIn 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.ResultsOur 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0172-x) contains supplementary material, which is available to authorized users.

Highlights

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
We evaluated the efficacy of cytokine adjuvant vaccine pulsed with inactivated CT26.WT colon tumor cells via measuring the tumor-specific Cytotoxic T cells (CTL) activity and associated anti-tumor effect in a colon cancer model
CT26.WT, a mouse colon adenocarcinoma cell line was purchased from the Shanghai Cell Biology Institutes, Chinese Academy of Sciences (Shanghai, China) and was cultured in RPMI medium 1640 (Hyclone, China) containing 10 % heat-inactivated fetal calf serum (FCS), 2 mmol/L glutamine, penicillin G (100U/mL), and streptomycin (100 μg/mL) at 37 °C in a humidified incubator supplemented with 5 % CO2

Summary

Introduction

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. Colon cancer is a common malignant tumor of the digestive tract [1]. It remains a challenge to treat advanced colon cancer due to postoperative recurrence and metastasis. Surgical resection of primary colorectal lesions combined with adjuvant chemotherapy and radiation continues as the mainstay of therapy [2]. The treatment with vaccines failed to significantly improve the 5-year survival of patients with colon cancer.

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Conclusion