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

• Published in: Journal of clinical oncology Vol. 22; no. 21; pp. 4272 - 4281
• Main Authors: STEINER, Hans Herbert, BONSANTO, Matteo Mario, BAUER, Harald, KIESSLING, Marika, KUNZE, Stefan, SCHIRRMACHER, Volker, HEROLD-MENDE, Christel, BECKHOVE, Philipp, BRYSCH, Michael, GELETNEKY, Karsten, AHMADI, Rezvan, SCHUELE-FREYER, Rebecca, KREMER, Paul, RANAIE, Golamreza, MATEJIC, Dejana
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-11-2004; Lippincott Williams & Wilkins
• Subjects: Avulavirus; Biological and medical sciences; Cancer Vaccines - pharmacology; Case-Control Studies; Central Nervous System Neoplasms - immunology; Central Nervous System Neoplasms - therapy; Feasibility Studies; Female; Glioblastoma - immunology; Glioblastoma - therapy; Humans; Immunohistochemistry; Immunotherapy, Active; Male; Medical sciences; Middle Aged; Neurology; Pilot Projects; Prognosis; Survival Rate; Tumor Cells, Cultured; Tumors; Tumors of the nervous system. Phacomatoses; Antineoplastic agent; Human; Prevention; Malignant glioma; Nervous system diseases; Cancerology; Vaccination; Central nervous system disease; Feasibility; Malignant tumor; Glioblastoma multiforme
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2004.09.038

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.
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.
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 (> or = 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.
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.