Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells.
Several reports of clinical trials of immunotherapy using dendritic cells have been published to date. In this study, we investigated the safety and clinical response of immunotherapy with fusions of dendritic and glioma cells for the treatment of patients with malignant glioma. Eight patients with malignant glioma, ranging in age from 4 to 63 years old, participated in this study. Dendritic cells were generated from peripheral blood. Cultured autologous glioma cells were established from surgical specimens in each case. Fusion cells of dendritic and glioma cells were prepared with polyethylene glycol, and the fusion efficiency ranged from 9.2 to 35.3% (mean, 21.9%). All patients received the fusion cells every three weeks for a minimum of 3, and a maximum of 7, immunizations. Fusion cells were injected intradermally, close to a cervical lymph node. The percentage of CD16- and CD56-positive cells in peripheral blood lymphocytes slightly increased after immunization in 4 out of 5 cases investigated. Peripheral blood mononuclear cells were incubated with irradiated autologous glioma or U87MG cells and supernatants were harvested. In 6 cases analyzed, the concentration of interferon-gamma in the supernatant increased after immunization. Clinical results showed that there were no serious adverse effects and two partial responses. Although the results of the phase I clinical trial of fusion cells indicated that this treatment safely induced immune responses. we were unable to establish a statistically significant treatment-associated response rate, due to the limited sample population. Therefore, further evaluation of the role of adjuvant cytokines is necessary.
Kikuchi
T
T
Department of Oncology, The Institute of DNA Medicine, Jikei University, Tokyo, Japan. tkikuchi@jikei.ac.jp
Akasaki
Y
Y
Irie
M
M
Homma
S
S
Abe
T
T
Ohno
T
T
D000328:Adult; D002459:Cell Fusion; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D007371:Interferon-gamma