Most of the current
tumor vaccines successfully elicit strong protection against
tumor but offer little
therapeutic effect against existing
tumors, highlighting the need for a more effective
vaccine strategy. Vaccination with
tumor antigen-presenting cells can induce antitumor immune responses. We have previously shown that NKT-licensed B cells prime cytotoxic T lymphocytes (CTLs) with
epitope peptide and generate prophylactic/therapeutic antitumor effects. To extend our B cell
vaccine approach to the whole
antigen, and to overcome the MHC restriction, we used a nonreplicating adenovirus to transduce B cells with antigenic gene. Primary B cells transduced with an adenovirus-encoding truncated Her-2/neu (AdHM) efficiently expressed Her-2/neu. Compared with the moderate antitumor activity induced by vaccination with adenovirus-transduced B cells (B/AdHM), vaccination with
alpha-galactosylceramide-loaded B/AdHM (B/AdHM/
alpha GalCer) induced significantly stronger antitumor immunity, especially in the
tumor-bearing mice. The depletion study showed that CD4(+), CD8(+) and NK cells were all necessary for the therapeutic immunity. Confirming the results of the depletion study, B/AdHM/
alpha GalCer vaccination induced cytotoxic NK cell responses but B/AdHM did not. Vaccination with B/AdHM/
alpha GalCer generated Her-2/neu-specific
antibodies more efficiently than B/AdHM immunization. More importantly, B/AdHM/
alpha GalCer could prime Her-2/neu-specific cytotoxic T cells more efficiently and durably than B/AdHM. CD4(+) cells appeared to be necessary for the induction of antibody and CTL responses. Our results demonstrate that, with the help of NKT cells,
antigen-transduced B cells efficiently induce innate immunity as well as a wide range of adaptive immunity against the
tumor, suggesting that they could be used to develop a novel cellular
vaccine.