BONE-MARROW-DERIVED DENDRITIC CELLS SERVE AS POTENT ADJUVANTS FOR PEPTIDE-BASED ANTITUMOR VACCINES

Dendritic cells (DCs) are considered the most effective antigen-presen ting cells (APCs) for primary immune responses, Since presentation of antigens to the immune system by appropriate professional APCs is crit ical to elicit a strong immune reaction and DCs seem to be quantitativ ely and functionally defective in the tumor host, DCs hold great premi se to improve cancer vaccines, Even though they are found in lymphoid organs, skin and mucosa, the difficulty of generating large numbers of DCs has been a major limitation for their use in vaccine studies, A s imple method for obtaining DCs from mouse bone marrow cells cultured i n the presence of GM-CSF + interleukin 4 is now available, In four dif ferent tumor models, mice injected with DCs grown in GM-CSF plus inter leukin 4 and prepulsed with a cytotoxic T lymphocyte-recognized tumor peptide epitope developed a specific cytotoxic T lymphocyte response a nd were protected against a subsequent tumor challenge with tumor cell s expressing the relevant tumor antigen, Moreover, treatment of day 5- 14 tumors with peptide-pulsed DCs resulted in sustained tumor regressi on in five different tumor models, These results suggest that presenta tion of tumor antigens to the immune system by professional APCs is a promising method to circumvent tumor-mediated immunosuppression and is the basis for ongoing clinical trials of cancer immunotherapy with tu mor peptide-pulsed DCs.