ABSTRACT
BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are aggressive tumors with poor 5-year survival rates, thus demanding new treatment concepts. METHODS: In a nonrandomized study, 20 HNSCC patients were preconditioned with interleukin (IL) 2 and subsequently vaccinated with virus-modified autologous tumor cells prepared from short-term tumor cultures. Antitumor reactivity was determined by delayed-type hypersensitivity (DTH) skin reaction. RESULTS: Preconditioning of tumor patients with IL-2 prior to vaccination was associated with an increased number of T cells especially after a radiation-induced marked decrease, and levels of mitogen stimulation capacity were almost as high as before surgery. MHC class I molecules expressing autologous tumor cell cultures were successfully infected. Vaccination with virus-modified tumor cells was able to increase systemic antitumor reactivity as revealed by augmentation of DTH reactivity to unmodified tumor cells. CONCLUSION: We provide evidence that a combination of preconditioning of HNSCC patients with IL-2 to improve their immune competence with subsequent vaccination with virus-modified autologous tumor cells leads to augmented antitumor DTH reactivity.
Subject(s)
Cancer Vaccines/administration & dosage , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/therapy , Newcastle disease virus/immunology , Adult , Cancer Vaccines/immunology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/mortality , Female , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/mortality , Humans , Immunotherapy, Active/methods , Interleukin-2/administration & dosage , Male , Middle Aged , Prognosis , Reference Values , Risk Assessment , Survival Analysis , Transplantation, Autologous , Treatment Outcome , Vaccination/methodsABSTRACT
Prognosis of patients with advanced head and neck squamous cell carcinomas (HNSCC) is still poor. Therefore, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe in HNSCC patients. Furthermore, we determined the influence on disease-free survival and overall survival and the vaccination-induced antitumor reactivity. In a nonrandomized pilot study, 20 patients were vaccinated postoperatively. Vaccine was prepared from the tumor cell cultures of patients by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and vaccine was applied up to five times. Antitumor immune reactivity was determined in the skin by delayed type hypersensitivity skin reaction and in the blood by enzyme-linked immunospot assay. Establishment of tumor cell cultures was successful in about 80% of the cases. After vaccination, we observed no severe side effects. Percentages of survival of vaccinated patients with stage III and stage IV tumors (n = 18) were 61% at 5 years. Immune monitoring revealed significant increases of antitumor delayed type hypersensitivity reactivity especially in disease-free patients, and in a significant proportion of vaccinated patients the presence of tumor-reactive T-cells in the peripheral blood even 5 to 7 years after the last vaccination. Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and may improve the prognosis of HNSCC patients with advanced tumors. This could be supported by antitumor immune responses that we observed especially in long-term surviving patients.
