Adoptive transfer of immature dendritic cells with autologous or allogeneic tumor cells generates systemic antitumor immunity

Dendritic cells (DCs) are potent antigen-presenting cells that are capable of priming systemic antitumor immune responses in animal tumor models. Howe ver, many of the model tumor systems tested need definition of the specific tumor antigens involved. To use DCs in situations that are more relevant t o the majority of human cancers, where the antigens are unknown, we have te sted the adoptive transfer of immature DCs in mouse colorectal and melanoma models of varying immunogenicity but with undefined antigens, When DCs adm ired with a syngeneic primary tumor inoculum were seeded s.c,, the growth o f the primary tumor was unchanged; however, if the primary tumor was then s urgically excised and the animal was rechallenged with the same tumor, sign ificant protection (75%) was generated when DCs were present in the origina l primary inoculum of a moderately immunogenic colorectal model (CMT93tk). This effect was not observed when a nonimmunogenic melanoma (B16) was teste d in an identical protocol. Next, DCs were injected directly into 6-9-mm es tablished tumors; again, protection (55%) was achieved against a secondary tumor challenge following excision of the primary, but only in the CMT93tk model of moderate immunogenicity, To increase the clinical relevance of thi s approach still further, we tested irradiated allogeneic K1735 melanoma ce lls mixed with syngeneic DCs as a vaccine against subsequent challenge with the poorly immunogenic syngeneic melanoma B16. The allogeneic vaccine alon e was ineffective, but, when admixed with DCs, a significant number of anim als rejected a subsequent B16 challenge, suggesting that DCs are able to pr ime an immune response against melanoma antigens shared between K1735 and B 16, The generation of systemic antitumor immunity by adoptive transfer of D Cs has significant clinical potential because it is technically straightfor ward and does not require the definition of specific tumor antigens.