期刊论文详细信息
Biological Procedures Online
Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen
Kuang-Wen Liao3  Ru-Ping Lee2  Chang-Jer Wu4  Shang-Chih Yang3  Yuan-Ting Hsieh3  Chi-Han Li3  Yu-Cheng Chen3  Shih-Han Kao3  Chen-Si Lin1 
[1]School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan
[2]Department of Nursing, Tzu Chi University, Hualien, Taiwan
[3]Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan
[4]Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
关键词: low-immunogenicity;    tumor vaccine;    tumor-derived peptide;    immunotherapy;   
Others  :  793281
DOI  :  10.1186/1480-9222-14-2
 received in 2011-11-14, accepted in 2012-02-03,  发布年份 2012
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【 摘 要 】

Background

It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development.

Results

To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone.

Conclusion

The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.

【 授权许可】

   
2012 Lin et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Reuschenbach M, von Knebel Doeberitz M, Wentzensen N: A systematic review of humoral immune responses against tumor antigens. Cancer Immunol Immunother 2009, 58:1535-1544.
  • [2]Hodge JW, Greiner JW, Tsang KY, Sabzevari H, Kudo-Saito C, Grosenbach DW, Gulley JL, Arlen PM, Marshall JL, Panicali D, Schlom J: Costimulatory molecules as adjuvants for immunotherapy. Front Biosci 2006, 11:788-803.
  • [3]Hallermalm K, Johansson S, Brave A, Ek M, Engstrom G, Boberg A, Gudmundsdotter L, Blomberg P, Mellstedt H, Stout R, et al.: Pre-clinical evaluation of a CEA DNA prime/protein boost vaccination strategy against colorectal cancer. Scand J Immunol 2007, 66:43-51.
  • [4]Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H, Li G: Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther 2008, 16:782-790.
  • [5]Ojima T, Iwahashi M, Nakamura M, Matsuda K, Nakamori M, Ueda K, Naka T, Ishida K, Primus FJ, Yamaue H: Successful cancer vaccine therapy for carcinoembryonic antigen (CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice. Int J Cancer 2007, 120:585-593.
  • [6]Wang YD, Sin WY, Xu GB, Yang HH, Wong TY, Pang XW, He XY, Zhang HG, Ng JN, Cheng CS, et al.: T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS. J Virol 2004, 78:5612-5618.
  • [7]Darji A, Guzman CA, Gerstel B, Wachholz P, Timmis KN, Wehland J, Chakraborty T, Weiss S: Oral somatic transgene vaccination using attenuated S. typhimurium. Cell 1997, 91:765-775.
  • [8]Sznol M, Lin SL, Bermudes D, Zheng LM, King I: Use of preferentially replicating bacteria for the treatment of cancer. J Clin Invest 2000, 105:1027-1030.
  • [9]Dougan G, Hormaeche CE, Maskell DJ: Live oral Salmonella vaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system. Parasite Immunol 1987, 9:151-160.
  • [10]Fagan PK, Djordjevic SP, Chin J, Eamens GJ, Walker MJ: Oral immunization of mice with attenuated Salmonella typhimurium aroA expressing a recombinant Mycoplasma hyopneumoniae antigen (NrdF). Infect Immun 1997, 65:2502-2507.
  • [11]Hormaeche DAAAACE (Ed): Molecular and Clinical Aspects of Bacterial Vaccine Development In 1995.
  • [12]Proskuryakov SY, Gabai VL: Mechanisms of tumor cell necrosis. Curr Pharm Des 2010, 16:56-68.
  • [13]Wright SD, Ramos RA, Patel M, Miller DS: Septin: a factor in plasma that opsonizes lipopolysaccharide-bearing particles for recognition by CD14 on phagocytes. J Exp Med 1992, 176:719-727.
  • [14]Russmann H, Shams H, Poblete F, Fu Y, Galan JE, Donis RO: Delivery of epitopes by the Salmonella type III secretion system for vaccine development. Science 1998, 281:565-568.
  • [15]Walker EB, Disis ML: Monitoring immune responses in cancer patients receiving tumor vaccines. Int Rev Immunol 2003, 22:283-319.
  • [16]Austin LM, Ozawa M, Kikuchi T, Walters IB, Krueger JG: The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol 1999, 113:752-759.
  • [17]Nakasone YFM, Matsushita T, Hamaguchi Y, Huu DL, Yanaba M, Sato S, Takehara K, Hasegawa M: Host-Derived MCP-1 and MIP-1α Regulate Protective Anti-Tumor Immunity to Localized and Metastatic B16 Melanoma. The American journal of pathology 2011.
  • [18]Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A: Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001, 19:683-765.
  • [19]Conti P, Kempuraj D, Kandere K, Di Gioacchino M, Barbacane RC, Castellani ML, Felaco M, Boucher W, Letourneau R, Theoharides TC: IL-10, an inflammatory/inhibitory cytokine, but not always. Immunol Lett 2003, 86:123-129.
  • [20]Wogensen L, Huang X, Sarvetnick N: Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans. J Exp Med 1993, 178:175-185.
  • [21]Wogensen L, Lee MS, Sarvetnick N: Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice. J Exp Med 1994, 179:1379-1384.
  • [22]Lee MS, Wogensen L, Shizuru J, Oldstone MB, Sarvetnick N: Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction. J Clin Invest 1994, 93:1332-1338.
  • [23]Moritani M, Yoshimoto K, Tashiro F, Hashimoto C, Miyazaki J, Ii S, Kudo E, Iwahana H, Hayashi Y, Sano T, et al.: Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice. Int Immunol 1994, 6:1927-1936.
  • [24]Anichini A, Mortarini R, Romagnoli L, Baldassari P, Cabras A, Carlo-Stella C, Gianni AM, Di Nicola M: Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with gammac cytokines. Blood 2006, 107:602-609.
  • [25]Chu Y, Xia M, Lin Y, Li A, Wang Y, Liu R, Xiong S: Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF. Cancer Gene Ther 2006, 13:510-519.
  • [26]Rammensee HG, Friede T, Stevanoviic S: MHC ligands and peptide motifs: first listing. Immunogenetics 1995, 41:178-228.
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