α‐Galactosylceramide‐loaded, antigen‐expressing B cells prime a wide spectrum of antitumor immunity

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 α‐galactosylceramide‐loaded B/AdHM (B/AdHM/αGalCer) 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/αGalCer vaccination induced cytotoxic NK cell responses but B/AdHM did not. Vaccination with B/AdHM/αGalCer generated Her‐2/ neu ‐specific antibodies more efficiently than B/AdHM immunization. More importantly, B/AdHM/αGalCer 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. © 2008 Wiley‐Liss, Inc.