Inhibiting p38 MAPK restored the ability of TCCM-treated BMDCs to immunize mice against tumor antigen and KLH and to prolong mouse survival. Immune responses monitored included titers of (A) anti-Id and (B) anti-KLH antibodies, measured by ELISA assays. Bars and values beside them represent the median titers of the antibodies. (C) Intracellular staining of IFN-γ- and IL-4-expressing T cells. Value in each graph represents the percentage of CD3+ T cells expressing IFN-γ or IL-4. (D) Cytotoxicity of spleen T cells from mice (5 per group) vaccinated with normal BMDCs, TCCM-treated (TCCM cells), TCCM- and SB203580 (SB)-treated (TCCM-cells+SB), and SB-treated cells (SB cells) pulsed with Id-KLH conjugates. Mice that had received injections of PBS served as a negative control group. (E) Survival curve of myeloma-bearing mice. Mice (5 per group) were first inoculated with 2 × 106 5TGM1 myeloma cells. Ten days later, when circulating IgG2b Id protein was increased 1.5- to 2-fold over the background level, mice received 3 weekly DC vaccinations, as indicated. Mice were humanely killed when moribund. Representative results of 3 experiments are shown.
