Enhancement of tumor lysate- and peptide-pulsed dendritic cell-based vaccines by the addition of foreign helper protein

We have evaluated whether the addition of a foreign helper protein, keyhole limpet hemocyanin (KLH), can augment the efficacy of tumor lysate-pulsed d endritic cells and peptide-pulsed DC immunizations in vivo. Besides being u sed as a "surrogate antigen" in approaches to measure immunological respons e in cancels patients, KLH is also an immunogenic carrier protein to elicit T-cell help. Using the D5 subline of B16 melanoma, we demonstrate that DCs pulsed with both KLH and tumor lysate mediate enhanced immune priming and rejection of established metastases in vivo, which is dependent on host-der ived T cells. Interleukin 2 augments the enhancement afforded by KLH, as me asured by cure rates and overall survival, in the absence of autoimmune dep igmentation. KLH added to DC immunizations markedly enhances tumor-specific T cell production of IFN-gamma. D5 melanoma exposed to similar levels of I FN-gamma results in substantial expression of MHC class I molecules. DCs pu lsed with KLH and mouse tyrosinase-related protein-2 peptide results in enh anced reduction of B16 melanoma metastases; the effect is most pronounced i n a setting where tyrosinase-related protein-2 peptide-pulsed DCs alone are completely ineffective. Collectively, these findings demonstrate that KLH addition to tumor antigen-pulsed DC immunizations can augment IFN-gamma pro duction and enhance in vivo antitumor activity.