alpha-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 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.
Kim
Yeon-Jeong
YJ
Laboratory of Immunology, College of Pharmacy, Seoul National University, Seoul, Korea.
Ko
Hyun-Jeong
HJ
Kim
Yun-Sun
YS
Kim
Dong-Hyeon
DH
Kang
Seock
S
Kim
Jong-Mook
JM
Chung
Yeonseok
Y
Kang
Chang-Yuil
CY
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D005699:Galactosylceramides / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide