Immunization with haptenized, autologous tumor cells induces inflammation of human melanoma metastases

Abstract

Twenty-four patients with metastatic melanoma were treated with a novel form of active immunotherapy, autologous tumor cell vaccine conjugated to the hapten, dinitrophenyl. This approach is based on the idea, well established in animal systems, that presentation of tumor antigens in the context of a strongly immunogenic hapten augments the development of immunity to those antigens. After being sensitized to dinitrophenyl, patients were given injections of dinitrophenyl-vaccine every 28 days following pretreatment with low dose cyclophosphamide. The vaccine induced a striking inflammatory response in superficial metastases in 14 of 24 patients, consisting of erythema, swelling, warmth, and tenderness over tumor masses. Immunohistochemistry and flow cytometric analysis of biopsy specimens showed marked infiltration with lymphocytes, the majority of which were CD8+, HLA-DR+ T-cells. These observations suggest that a T-cell-mediated immune response against melanoma-associated antigens was facilitated by the "helper" effect of the anti-hapten response.