Background: An autologous vaccine of apoptotic tumor cells (ATC) & dendritic cells (DC) was administered to stage III/IV HNSCC patients to study safety and feasibility. Methods: Autologous DC were generated from monocytes, loaded with ATC and delivered intranodally. Delayed-type hypersensitivity (DTH) and immunological endpoints were measured pre/post vaccination. Clinical follow-up was required. Results: Tumors obtained from 30 patients yielded 2x10(6) - 2x10(8) tumor cells. Only 19/30 (63%) were sterile. 10/30 patients (33%) had ≥1x10(7) sterile tumor cells required for vaccine production. 8/10 had positive recall DTH. 5/10 were leukapheresed to generate DC. 4/5 were vaccinated. ATC-reactive T cells were detected in 3/4 patients. All 4 survived > 5 years. The trial failed to enroll the projected 12 patients and was terminated. Conclusions: This vaccine was safe and immunogenic but feasible only in HNSCC patients with positive pre-vaccine DTH and ≥1x10(7) sterile tumor cells. All vaccinated patients were long-term disease-free survivors. [Words, 150] This article is protected by copyright. All rights reserved.