We have shown that Flk2/
Flt3 ligand (Flt3L)-transduced
tumor vaccine induces transferable T cell protection against a murine
breast cancer cell line, but a direct comparison with the potent effector
GM-CSF, the activity against preestablished
tumors, and the mechanism of antitumor response in this
breast cancer model are not known. We compared vaccination with C3L5 cells expressing Flt3L (C3Lt-Flt3L) and
GM-CSF (C3L5-GMCSF) by injecting 1 x 10(4) cells subcutaneously into the chest wall and then, after 4 weeks, challenging the contralateral chest of
tumor-free mice with parental C3L5 cells. C3L5-Flt3L and C3L5-GMCSF had reduced in vivo growth rates (25%
tumor formation each) compared with 100%
tumor formation of C3L5 cells expressing only
neomycin phosphotransferase (C3L5-G1N). However, when
tumor-free animals were challenged with parental C3L5 cells, C3L5-Flt3L vaccination was significantly better at preventing
tumor growth (p < 0.05) than C3L5-GMCSF vaccination (33% of C3L5-Flt3L-vaccinated animals developed
tumor compared with 77% of C3L5-GMCSF-vaccinated animals). Adoptive transfer of immunity for both
vaccines was demonstrated; splenic T cells from
tumor-free mice protected naive mice from parental
tumor challenge. To simulate minimal disease, parental C3L5 cells at two concentrations (high, 5 x 10(3) cells; or low, 1 x 10(3) cells) were injected into the contralateral chest wall 4 days prior to treatment with C3L5-G1N or C3L5-Flt3L. C3L5-Flt3L treatment decreased contralateral parental
tumor formation (high, 67%
tumor free; low, 90%
tumor free) compared with C3L5-G1N treatment (high and low, 0%
tumor free). Immunodepletion of activated natural killer cells with anti-asialo-GM1 blocked C3L5-Flt3L- and C3L5 plus soluble Flt3L-mediated antitumor activity. Thus, Flt3L-transduced
tumor cells manifest potent antitumor activity, apparently mediated, at least partially, by natural killer cells.