Originally published as JCO Early Release 10.1200/JCO.2004.06.043 on December 22 2003

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Immunopharmacologic Analysis of an Autologous, Hapten-Modified Human Melanoma Vaccine

From the Department of Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Address reprint requests to David Berd, MD, Thomas Jefferson University, 1015 Walnut St, Suite 1024, Philadelphia, PA 19107; e-mail: d_berd{at}mail.jci.tju.edu

PURPOSE: We have previously reported a clinical trial of a human cancer vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), in patients with clinical stage III melanoma. Here we present a follow-up report expanded to 214 patients with 5-year follow-up.

PATIENTS AND METHODS: Two hundred fourteen patients with clinical stage III melanoma (117 patients with stage IIIC and 97 patients with stage IIIB) who were melanoma-free after standard lymphadenectomy were treated with multiple intradermal injections of autologous, DNP-modified vaccine mixed with bacille Calmette-Guérin. Four vaccine dosage schedules were tested sequentially, all of which included low-dose cyclophosphamide. Patients were tested for delayed-type hypersensitivity (DTH) to autologous melanoma cells, both DNP-modified and unmodified, and to control materials.

RESULTS: The 5-year overall survival (OS) rate of the 214 patients was 44%. DTH responses to unmodified autologous melanoma were induced in 47% of patients. The OS of this DTH-positive group was double that of DTH-negative patients (59.3% v 29.3%; P < .001). In contrast, positive DTH responses to DNP-modified autologous melanoma cells and to purified protein derivative developed in almost all patients but did not affect OS. Surprisingly, the OS after relapse was also significantly longer in patients who developed positive DTH to unmodified tumor cells (25.2% v 12.3%; P < .001). Finally, the development of DTH was dependent on the schedule of administration of the vaccine, specifically, the timing of an induction dose administered at the beginning of the treatment program.

CONCLUSION: This study underscores the importance of the immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to other cancer vaccine technologies.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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