Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

Gene Ther. 2014 Jan;21(1):106-14. doi: 10.1038/gt.2013.65. Epub 2013 Nov 14.


For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology
  • Cancer Vaccines* / immunology
  • Cells, Cultured
  • Dependovirus / genetics*
  • Dependovirus / metabolism
  • Female
  • Genetic Vectors
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunotherapy
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Natural Killer T-Cells / immunology
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Xenograft Model Antitumor Assays


  • Cancer Vaccines
  • HLA-A2 Antigen
  • ERBB2 protein, human
  • Receptor, ErbB-2