Dendritic cells capture killed tumor cells and present their antigens to elicit tumor-specific immune responses

Due to their capacity to induce primary immune responses, dendritic cells ( DC) are attractive vectors for immunotherapy of cancer. Yet the targeting o f tumor Ags to DC remains a challenge. Here we show that immature human mon ocyte-derived DC capture various killed tumor cells, including Jurkat T cel l lymphoma, malignant melanoma, and prostate carcinoma. DC loaded with kill ed tumor cells induce MHC class I- and class ii-restricted proliferation of autologous CD8(+) and CD4(+) T cells, demonstrating cross-presentation of tumor cell-derived Ags. Furthermore, tumor-loaded DG elicit expansion of CT L with cytotoxic activity against the tumor cells used for immunization. CT L elicited by DC loaded with the PC3 prostate carcinoma cell bodies kill an other prostate carcinoma cell line, DU145, suggesting recognition of shared Ags. Finally, CTL elicited by DC loaded with killed LNCap prostate carcino ma cells, which express prostate specific Ag (PSA), are able to kill PSA pe ptide-pulsed T2 cells, This demonstrates that induced CTL activity is not o nly due to alloantigens, and that alloantigens do not prevent the activatio n of T cells specific for tumor-associated Ags, This approach opens the pos sibility of using allogeneic tumor cells as a source of tumor Ag for antitu mor therapies.