We have evaluated whether the addition of a foreign helper
protein,
keyhole limpet hemocyanin (KLH), can augment the efficacy of
tumor lysate-pulsed dendritic cells and
peptide-pulsed DC immunizations in vivo. Besides being used as a "surrogate
antigen" in approaches to measure immunological response in
cancer 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-derived T cells.
Interleukin 2 augments the enhancement afforded by KLH, as measured by cure rates and overall survival, in the absence of autoimmune depigmentation. KLH added to DC immunizations markedly enhances
tumor-specific T cell production of IFN-gamma. D5
melanoma exposed to similar levels of IFN-gamma results in substantial expression of
MHC class I molecules. DCs pulsed with KLH and mouse
tyrosinase-related protein-2 peptide results in enhanced reduction of
B16 melanoma metastases; the effect is most pronounced in 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 production and enhance in vivo antitumor activity.