Enhanced antitumor immunity derived from a novel vaccine of fusion hybrid between dendritic and engineered myeloma cells.
OBJECTIVE
Dendritic cell-tumor cell fusion hybrid vaccines which facilitate antigen presentation represent a new powerful strategy in cancer immunotherapy. The clinical frequency of objective responses to the conventional fusion hybrid vaccines is still quite low, indicating that the current conventional protocol of simply fusing dendritic cells (DCs) and tumor cells needs further improvement to enhance its antitumor efficiency.


METHODS
In the present study, we generated a novel fusion hybrid DC/J558(CD40L) by fusing DCs and an engineered J558(CD40L) myeloma cells expressing CD40 ligand (CD40L) molecule using polyethylene glycol (PEG). The fusion efficiency was approximately 20%. We investigated the antitumor immunity derived from vaccination of the fusion hybrid DC/J558(CD40L).


RESULTS
Our results showed that vaccination of mice with DC/J558(CD40L) hybrids induced more efficient cytotoxic T lymphocyte (CTL) responses and protective immunity against J558 tumor cells, than that of the conventional fusion hybrid DC/J558 from the fusion of DCs and J558 tumor cells. The antitumor immunity derived from vaccination of DC/J558(CD40L) was mainly mediated by CD4(+) and CD(8+)cT cells, but not natural killer (NK) cells.


CONCLUSIONS
Therefore, this novel fusion hybrid vaccine which combines gene-modified tumor and DC vaccines may be an attractive strategy for cancer immunotherapy.
Hao
Siguo
S
Health Research Divison, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan S7N 4H4, Canada.
Bi
Xuguang
X
Xu
Shuling
S
Wei
Yangdou
Y
Wu
Xiaochu
X
Guo
Xuling
X
Carlsen
Svein
S
Xiang
Jim
J
D000818:Animals; D000917:Antibody Formation; D023201:CD40 Ligand / Q000096:biosynthesis / Q000235:genetics; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy / Q000639:trends; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D023201:CD40 Ligand