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Immunization with Haptenized, Autologous Tumor Cells Induces Inflammation of Human Melanoma Metastases¹

Thomas Jefferson University, Division of Medical Oncology, Philadelphia 19107 [D. B., H. C. M., M. J. M.], and the University of Pennsylvania School of Medicine, Department of Dermatology, Philadelphia, Pennsylvania 19104 [G. M.]

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.

¹ This work was supported by NIH Grants CA 39248, CA 40358, and AR 39674 from the NIH and by funds from the Nat Pincus Trust and the Rae S. Uber Trust.

² To whom requests for reprints should be addressed, at Division of Medical Oncology, Thomas Jefferson University, 1015 Walnut Street, Suite 1005, Philadelphia, PA 19107.

Received 2/25/91. Accepted 3/28/91.

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