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
Deep Link:
http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=1674
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