Antitumor Vaccination of Patients With Glioblastoma Multiforme: A Pilot Study to Assess Feasibility, Safety, and Clinical Benefit
| Autor: | Harald Bauer, Hans H. Steiner, Marika Kiessling, Stefan Kunze, Karsten Geletneky, Michael Brysch, Rezvan Ahmadi, Dejana Matejic, P. Kremer, Golamreza Ranaie, Volker Schirrmacher, Philipp Beckhove, Rebecca Schuele-Freyer, Christel Herold-Mende, Matteo M. Bonsanto |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Oncolytic Newcastle Disease Virus Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment Pilot Projects Cancer Vaccines Newcastle disease Virus Central Nervous System Neoplasms Internal medicine Autologous Tumor Cell Vaccine Tumor Cells Cultured medicine Humans Avulavirus Survival rate biology business.industry ELISPOT Immunotherapy Active Immunotherapy Middle Aged Prognosis biology.organism_classification Immunohistochemistry Survival Rate Vaccination Case-Control Studies Immunology Feasibility Studies Female Glioblastoma business |
| Zdroj: | Journal of Clinical Oncology. 22:4272-4281 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2004.09.038 |
| Popis: | 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 (≥ 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the 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 glioblastomas. This could be substantiated by the observed antitumor immune response. |
| Databáze: | OpenAIRE |
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