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Granulocyte-Macrophage Colony-Stimulating Factor-Based Melanoma Cell Vaccines Immunize Syngeneic and Allogeneic Recipients via Host Dendritic Cells ¹

Achim Schneeberger^2,*, Petra Lührs^*, Raphaela Kutil^*, Peter Steinlein, Hansjörg Schild, Walter Schmidt and Georg Stingl^*

^* Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Vienna, Austria; Institute for Molecular Pathology, Vienna, Austria; Institute of Immunology, University of Tübingen, Morgenstelle, Tübingen, Germany; and Intercell, Vienna, Austria

Subcutaneous injection of GM-CSF-expressing cancer cells into experimental animals results in protective cancer immunity. To delineate the mode of action of such vaccines, we used trinitrophenyl, the antigenic moiety of the contact allergen trinitrochlorobenzene, as surrogate Ag. Trinitrophenyl-derivatized bone marrow-derived dendritic cells were found to elicit a contact hypersensitivity response in syngeneic, but not in allogeneic recipients, compatible with their expected mode of direct Ag presentation. When expressing GM-CSF, haptenized M3 melanoma cells were also able to induce a contact hypersensitivity response but, in contrast to bone marrow-derived dendritic cells, not only in syngeneic but also in allogeneic recipients. This argues for a critical role of host APC. To identify their nature, we introduced the -galactosidase (gal) gene into M3-GM cells. Their administration activated gal-specific, L^d-restricted CTL in syngeneic BALB/c mice. Evaluation of lymph nodes draining M3-GM-gal injection sites revealed the presence of cells presenting the respective L^d-binding gal peptide epitope. Based on their capacity to activate gal-specific CTL, they were identified as being CD11c⁺ dendritic cells. These experiments provide a rational basis for the use of GM-CSF-based melanoma cell vaccines in an allogeneic setting.