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  • 1
    Keywords: brain ; CELLS ; EXPRESSION ; SURVIVAL ; tumor ; TUMOR-CELLS ; BLOOD ; CELL ; Germany ; THERAPY ; DISEASE ; LONG-TERM ; TUMORS ; TIME ; PATIENT ; INFECTION ; prognosis ; SKIN ; T cell ; T cells ; T-CELL ; T-CELLS ; cell culture ; culture ; MEMORY ; virus ; NERVOUS-SYSTEM ; NO ; immunohistochemistry ; ASSAY ; NUMBER ; VACCINE ; SAFETY ; CD8(+) ; immune response ; IMMUNE-RESPONSE ; IMMUNITY ; T-LYMPHOCYTES ; vaccination ; T lymphocyte ; side effects ; NEWCASTLE-DISEASE VIRUS ; ESTABLISHMENT ; TUMOR CELLS ; LONG-TERM SURVIVORS ; GLIOMAS ; T lymphocytes ; IMMUNIZATION ; ONCOLOGY ; AUTOLOGOUS TUMOR ; overall survival ; NEWCASTLE-DISEASE-VIRUS ; SURVIVORS
    Abstract: Purpose Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. Patients and Methods In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. Results Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P =.024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P 〈.001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (greater than or equal to3 years). Ninety-one percent of vaccinated 39% survived 2 years, and 4% were long-term survivors. In the patients survived I year, vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. Conclusion Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with gliobiastomas. This could be substantiated by the observed antitumor immune response. (C) 2004 by American Society of Clinical Oncology
    Type of Publication: Journal article published
    PubMed ID: 15452186
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  • 2
    Keywords: CANCER ; CELLS ; EXPRESSION ; SURVIVAL ; tumor ; TUMOR-CELLS ; BLOOD ; carcinoma ; CELL ; Germany ; THERAPY ; DISEASE ; LONG-TERM ; TUMORS ; TIME ; PATIENT ; RESPONSES ; INFECTION ; prognosis ; INDUCTION ; SKIN ; T cell ; T cells ; T-CELL ; T-CELLS ; cell culture ; culture ; IMMUNE-RESPONSES ; virus ; NO ; STAGE ; ASSAY ; LYMPHOCYTES ; HEAD ; VACCINE ; CARCINOMAS ; NECK ; squamous cell carcinoma ; immune response ; IMMUNE-RESPONSE ; vaccination ; CANCER-RESEARCH ; side effects ; head and neck ; PERIPHERAL-BLOOD ; ESTABLISHMENT ; CELL CARCINOMA ; overall survival ; CANCER STATISTICS ; ACTIVE-SPECIFIC IMMUNOTHERAPY ; IMMUNE SUPPRESSION ; MURINE MODEL ; NEWCASTLE-DISEASE-VIRUS
    Abstract: 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
    Type of Publication: Journal article published
    PubMed ID: 15520216
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