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[Cancer Research 61, 2618-2624, March 15, 2001]
© 2001 American Association for Cancer Research

Immunology

Enhancement of Tumor Lysate- and Peptide-pulsed Dendritic Cell-based Vaccines by the Addition of Foreign Helper Protein1

Koichi Shimizu, Elaine K. Thomas, Martin Giedlin and James J. Mulé2

Departments of Surgery [K. S., J. J. M.] and Internal Medicine [J. J. M.], and the Tumor Immunology and Immunotherapy Program of the Comprehensive Cancer Center [J. J. M.], University of Michigan Medical Center, Ann Arbor, Michigan 48103-0666; Extramural Research, Immunex Corporation, Seattle, Washington 98101 [E. K. T.]; and Vaccines and Gene Therapy Research, Chiron Technologies, 4560 Horton Street, Emeryville, California 94608-2916 [M. G.]

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.




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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