alpha-Galactosylceramide-loaded, antigen-expressing B cells prime a wide spectrum of antitumor immunity.
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| Abstract |
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.
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| Authors | Yeon-Jeong Kim, Hyun-Jeong Ko, Yun-Sun Kim, Dong-Hyeon Kim, Seock Kang, Jong-Mook Kim, Yeonseok Chung, Chang-Yuil Kang |
| Journal | International journal of cancer (Int J Cancer) Vol. 122 Issue 12 Pg. 2774-83 (Jun 15 2008) ISSN: 1097-0215 [Electronic] United States |
| PMID | 18338753 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | (c) 2008 Wiley-Liss, Inc. |
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