INDUCTION OF ANTITUMOR IMMUNITY USING BONE MARROW-GENERATED DENDRITICCELLS

We have previously shown that bone marrow-generated dendritic cells (D C) pulsed with a class I-restricted peptide are potent inducers of CD8 (+) CTL, In the present study we have investigated whether bone marrow -generated DC are capable of inducing antitumor immunity, We show that a single immunization with DC pulsed with OVA peptide was highly effe ctive in eliciting a protective immune response against a challenge wi th tumor cells expressing the OVA gene (E.G7-OVA), more so than immuni zation with irradiated E.G7-OVA cells, OVA peptide-pulsed RMA-S cells, or free OVA peptide mixed with adjuvant, The addition of free OVA pro tein to day 4 or day 7 bone marrow cultures, but not to day 9 mature D C, was also effective in eliciting CTL and engendering antitumor immun ity, but was less effective than peptide-pulsed DC, Induction of CTL a nd antitumor immunity by bone marrow-generated DC pulsed with the clas s I-restricted OVA peptide correlated with the expression of syngeneic MHC class II molecules on the DC, This and the fact that induction of tumor immunity was dependent on CD4(+) T cells suggest that in vivo p riming of CTL and induction of antitumor immunity by bone marrow-gener ated DC also require the presentation of MHC class II-restricted epito pes and activation of CD4(+) T cells, This observation has potentially important implications to the use of peptide-pulsed DC in clinical im munotherapy.