Originally published as JCO Early Release 10.1200/JCO.2004.09.038 on September 27 2004

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Antitumor Vaccination of Patients With Glioblastoma Multiforme: A Pilot Study to Assess Feasibility, Safety, and Clinical Benefit

From the Departments of Neurosurgery, Head and Neck Surgery, Neuropathology, and Neuroanaesthetics, University of Heidelberg; and Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany

Address reprint requests to Hans Herbert Steiner, MD, Department of Neurosurgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; e-mail: hsteiner{at}med.uni-heidelberg.de

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.

Presented in part at the following conferences: European Association of Neuro-Oncology, Florence, Italy, September 7-10, 2002; Deutsche Gesellschaft für Neurologie, Mannheim, Germany, September 25-29, 2002; Deutsche Gesellschaft für Neurochinurgie, Saarbrücken, Germany, May 25-28, 2003; and the 15th International Conference on Brain Tumor Research and Therapy, Sorrento, Italy, May 24-27, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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