ELICITING T-CELL IMMUNITY AGAINST POORLY IMMUNOGENIC TUMORS BY IMMUNIZATION WITH DENDRITIC CELL-TUMOR FUSION VACCINES

Dendritic cells (DCs) are the most effective APCs and are being studie d as natural adjuvants or Ag delivery vehicles to elicit T cell-mediat ed antitumor immunity. This study examined whether inoculation of DCs fused with poorly immunogenic tumor cells elicited tumor-reactive T ce lls for adoptive immunotherapy, DCs derived from bone marrow of C57BL/ 6 (B6) mice were fused with syngeneic B16 melanoma or RMA-S lymphoma c ells by polyethylene glycol. The B16/DC and RMA-S/DC fusion hybrids ex pressed MHC class I, class II Ags, costimulatory molecules, as well as DC-specific and tumor-derived surface markers. The tumor/DC hybrids w ere capable of processing and presenting tumor-derived Ags, and immuni zation of B6 mice with irradiated B16/DC or RMA-S/DC vaccine elicited tumor-specific CTL activities. Vaccination of BG mice with irradiated B16/DC fusion preparations induced partial host protective immunity ag ainst B16 tumor challenge. Reduced tumor incidence and prolonged survi val time were observed, Adoptive transfer of T cells derived from B16/ DC vaccine-primed lymph nodes into B16 tumor-bearing mice greatly redu ced the number of established pulmonary metastases with or without in vivo administration of IL-2, Moreover, adoptive transfer of RMA-S/DC v accine-primed, cultured lymph node T cells eradicated disseminated FBL -3 tumor. The results demonstrate that tumor/DC fusion products are ef fective cellular vaccines for eliciting T cell-mediated antitumor immu nity.