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Departments of
*
Immunology and
Cellular Biology, Second Military Medical University, Shanghai, People’s Republic of China, and
Department of Molecular Biotherapy Research, Japanese Foundation of Cancer Research, Toshima-ku, Tokyo, Japan
Dendritic cells (DC) are regarded as attractive candidates for
cancer immunotherapy. Our aim is to improve the therapeutic efficacy of
DC-based tumor vaccine by augmenting DC preferential chemotaxis on T
cells. Mouse bone marrow-derived DC were transduced with lymphotactin
(Lptn) gene by adenovirus vector. The supernatants from Lptn
gene-modified DC (Lptn-DC) were capable of attracting CD4+
and CD8+ T cells in a chemotaxis assay, whereas their mock
control could not. Lptn expression of Lptn-DC was further confirmed by
RT-PCR. Lptn-DC were pulsed with Mut1 peptide and used for vaccination.
Immunization with the low dose (1 x 104) of Mut1
peptide-pulsed DC induced weak CTL activity, whereas the same amounts
of Mut1 peptide-pulsed Lptn-DC markedly induced specific CTL against
3LL tumor cells. A single immunization with 1 x 104
Mut1 peptide-pulsed Lptn-DC could render mice resistant to a 5 x
105 3LL tumor cell challenge completely, but their
counterpart could not. The protective immunity induced by Mut1
peptide-pulsed Lptn-DC depends on both CD4+ T cells and
CD8+ T cells rather than NK cells in the induction phase
and depends on CD8+ T cells rather than CD4+ T
cells and NK cells in the effector phase. Moreover, the involvement of
CD28/CTLA4 costimulation pathway and IFN-
are also necessary.
When 3LL tumor-bearing mice were treated with 1 x 104
Mut1 peptide-pulsed Lptn-DC, their pulmonary metastases were
significantly reduced, whereas the same low dose of Mut1 peptide-pulsed
DC had no obvious therapeutic effects. Our data suggest that Lptn-DC
are more potent adjuvants for peptide delivery to induce protective and
therapeutic antitumor immunity.
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