Clinical Evaluation of Dendritic Cell Vaccination for Patients with Recurrent Glioma: Results of a Clinical Phase I/II Trial

• Published in: Clinical cancer research 2005-06, Vol.11 (11), p.4160-4167
• Main Authors: YAMANAKA, Ryuya, HOMMA, Junpei, TANAKA, Ryuichi, YAJIMA, Naoki, TSUCHIYA, Naoto, SANO, Masakazu, KOBAYASHI, Tsutomu, YOSHIDA, Seiichi, ABE, Takashi, NARITA, Miwako, TAKAHASHI, Masuhiro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Dendritic Cell; Dendritic Cells - immunology; Female; Glioma; Glioma - mortality; Glioma - pathology; Glioma - therapy; Humans; Immunotherapy; Immunotherapy, Adoptive - methods; Injections, Intradermal; Injections, Intralesional; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local; Neurology; Pharmacology. Drug treatments; Survival Rate; Treatment Outcome; Tumors of the nervous system. Phacomatoses
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-0120

Purpose: To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma. Experimental Design: Twenty-four patients with recurrent malignant glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II clinical study of dendritic cell therapy. All patients were resistant to the standard maximum therapy. The patient's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor, plus interleukin 4 with or without OK-432, and pulsed with an autologous tumor lysate. Dendritic cells were injected intradermally, or both intratumorally and intradermally every 3 weeks. Results: The protocols were well tolerated with only local redness and swelling at the injection site in several cases. Clinical responses were as follows: 1 patient with partial response, 3 patients with minor response, 10 patients with stable disease, and 10 patients with progressive disease. The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation. The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only. Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination. The overall survival of patients with grade 4 glioma was 480 days, which was significantly better than that in the control group. Conclusions: This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma. Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients.