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

• DOI: 10.1200/jco.2004.09.038
• Publication Date: 2004-09-28T00:15:27Z
• Authors: Hans Herbert Steiner; Matteo Mario Bons...; Philipp Beckhove; Michael Brysch; Karsten Geletneky; Rezvan Ahmadi; Rebecca Schuele-F...; Paul Kremer; Golamreza Ranaie; Dejana Matejic; Harald Bauer; Marika Kiessling; Stefan Kunze; Volker Schirrmacher; Christel Herold-M...
• Keywords: Male; Immunotherapy, Active; Pilot Projects; Middle Aged; Prognosis; Cancer Vaccines; Immunohistochemistry; 3. Good health; Central Nervous System Neoplasms; Survival Rate; 03 medical and health sciences; 0302 clinical medicine; Case-Control Studies; Tumor Cells, Cultured; Feasibility Studies; Humans; Female; Avulavirus; Glioblastoma

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.