Generation of fusion protein EGFRvIII-HBcAg and its anti-tumor effect in vivo.
The epidermal growth factor receptor variant III (EGFRvIII) is the most common variation of EGFR. Because it shows a high frequency in several different types of tumor and has not been detected in normal tissues, it is an ideal target for tumor specific therapy. In this study, we prepared EGFRvIII-HBcAg fusion protein. After immunization with fusion protein, HBcAg or PBS, the titers of antibody in BALB/c mice immunized with fusion protein reached 2.75 x 10(5). Western blot analysis demonstrated that the fusion protein had specific antigenicity against anti-EGFRvIII antibody. Further observation showed fusion protein induced a high frequency of IFN-gamma-secreting lymphocytes. CD4+T cells rather than CD8+T cells were associated with the production of IFN-gamma. Using Renca-vIII(+) cell as specific stimulator, we observed remarkable cytotoxic activity in splenocytes from mice immunized with fusion protein. Mice were challenged with Renca-vIII(+) cells after five times immunization. In fusion protein group, three of ten mice failed to develop tumor and all survived at the end of the research. The weight of tumors in fusion protein were obviously lighter than that in other two groups (t = 4.73, P = 0.044; t = 6.89, P = 0.040). These findings demonstrated that EGFRvIII-HBcAg fusion protein triggered protective responses against tumor expressing EGFRvIII.
Department of Nuclear Medicine, First affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. duanxy@mail.xjtu.edu.cn
Xiao-yi
XY
Duan
Dong-gang
DG
Han
Ming-xin
MX
Zhang
Jian-sheng
JS
Wang
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000276:immunology* / Q000627:therapeutic use; D006512:Hepatitis B Core Antigens / Q000276:immunology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use
D019496:Cancer Vaccines; D006512:Hepatitis B Core Antigens; D011993:Recombinant Fusion Proteins; C410723:epidermal growth factor receptor VIII; D007371:Interferon-gamma; D066246:ErbB Receptors