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The anti-tumor immune responses induced by a fusion protein of ovarian carcinoma anti-idiotypic antibody 6B11ScFv and murine GM-CSF in BALB/c mice
  1. H. Cui,
  2. X.-H. Chang,
  3. B. Liu,
  4. J. Feng,
  5. Y. Li,
  6. X. Ye,
  7. S.-J. Cao,
  8. T.-Y. Fu,
  9. Y. Yao,
  10. H.-N. Qian and
  11. H.-Q. Li
  1. Gynecologic Oncology Center, Peking University People's Hospital, Beijing, P.R. China
  2. Jenner Biotech Institute, Tianjin, R.O. China
  1. Address correspondence and reprint requests to: Heng Cui, Gynecologic Oncology Center, Peking University People's Hospital, Beijing, R.O. China. E-mail: cuiheng20{at}tom.com.

Abstract

Ovarian carcinoma anti-idiotypic antibody 6B11 was murine derived; we previously have cloned 6B11 single-chain Fv antibody (6B11ScFv) and constructed the 6B11ScFv/human granulocyte-macrophage colony stimulating factor (GM-CSF) fusion protein (designated as 6B11GM) to enhance the immunogenecity of the single-chain Ab2. Because of the difference in species specificity between human GM-CSF and murine GM-CSF, there is no immune competent animal model on which the effect and metabolism of 6B11GM as a vaccine could be observed. In this study, 6B11mGM fusion gene was constructed by the fusing murine GM-CSF cDNA gene with 6B11ScFv. The fusion gene was cloned and expressed. The product of this gene is a fusion protein. It could specifically interact with the primary anti-ovarian carcinoma monoclonal antibody (COC166-9) and rat anti-mouse GM-CSF monoclonal antibody, respectively, and stimulate the growth of NFS-60 cells (a murine GM-CSF-dependent cell line). The specific anti-tumor immune response could be induced in BALB/c mice after immunized with anti-idiotypic fusion protein instead of ovarian carcinoma antigen without carrier proteins and adjuvant. Ab3 could be detected in the sera of immunized mice with 6B11mGM by enzyme-linked immunoadsorbent assay test. Moreover, the fusion protein stimulated proliferation of CD4+ T cell from the spleen of BALB/c mice and proliferation of CD8+ T cell to a lesser degree. Therefore, 6B11mGM probably induces both humoral and cellular immunity against ovarian carcinoma in vivo.

  • antibody
  • anti-idiotype
  • ovarian carcinoma
  • recombinant fusion protein
  • tumor vaccine

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