Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial

被引:204
作者
Yamanaka, R
Abe, T
Yajima, N
Tsuchiya, N
Tsuchiya, N
Homma, J
Kobayashi, T
Narita, M
Takahashi, M
Tanaka, R
机构
[1] Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 9518585, Japan
[2] Niigata Univ, Sch Med, Dept Internal Med 1, Niigata, Japan
关键词
glioma; dendritic cell; immunotherapy; ELISPOT assay;
D O I
10.1038/sj.bjc.6601268
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In this Phase I/II trial, the patient's peripheral blood dendritic cells were pulsed with an autologous tumour lysate of the glioma. Seven patients with glioblastoma and three patients with anaplastic glioma, ranging in age from 20 to 69 years, participated in this study. The mean numbers of vaccinations of tumour lysate-pulsed dendritic cells were 3.7 times intradermally close to a cervical lymph node, and 3.2 times intratumorally via an Ommaya reservoir. The percentage of CD56-positive cells in the peripheral blood lymphocytes increased after immunisation. There were two minor responses and four no-change cases evaluated by radiological findings. Dendritic cell vaccination elicited T-cell-mediated antitumour activity, as evaluated by the ELISPOT assay after vaccination in two of five tested patients. Three patients showed delayed-type hypersensitivity reactivity to the autologous tumour lysate, two of these had a minor clinical response, and two had an increased ELISPOT result. Intratumoral CD4+ and CD8+ T-cell infiltration was detected in two patients who underwent reoperation after vaccination. This study demonstrated the safety and antitumour effects of autologous tumour lysate-pulsed dendritic cell therapy for patients with malignant glioma.
引用
收藏
页码:1172 / 1179
页数:8
相关论文
共 33 条
[1]   Antitumor effect of immunizations with fusions of dendritic and glioma cells in a mouse brain tumor model [J].
Akasaki, Y ;
Kikuchi, T ;
Homma, S ;
Abe, T ;
Kofe, D ;
Ohno, T .
JOURNAL OF IMMUNOTHERAPY, 2001, 24 (02) :106-113
[2]   Dendritic cells pulsed with tumor extract-cationic liposome complex increase the induction of cytotoxic T lymphocytes in mouse brain tumor [J].
Aoki, H ;
Mizuno, M ;
Natsume, A ;
Tsugawa, T ;
Tsujimura, K ;
Takahashi, T ;
Yoshida, J .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2001, 50 (09) :463-468
[3]   Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo [J].
Boczkowski, D ;
Nair, SK ;
Snyder, D ;
Gilboa, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) :465-472
[4]   PRODUCTION OF IL-10 BY MELANOMA-CELLS - EXAMINATION OF ITS ROLE IN IMMUNOSUPPRESSION MEDIATED BY MELANOMA [J].
CHEN, QY ;
DANIEL, V ;
MAHER, DW ;
HERSEY, P .
INTERNATIONAL JOURNAL OF CANCER, 1994, 56 (05) :755-760
[5]  
CONSTAM DB, 1992, J IMMUNOL, V148, P1404
[6]   VACCINATION WITH IRRADIATED TUMOR-CELLS ENGINEERED TO SECRETE MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR STIMULATES POTENT, SPECIFIC, AND LONG-LASTING ANTITUMOR IMMUNITY [J].
DRANOFF, G ;
JAFFEE, E ;
LAZENBY, A ;
GOLUMBEK, P ;
LEVITSKY, H ;
BROSE, K ;
JACKSON, V ;
HAMADA, H ;
PARDOLL, D ;
MULLIGAN, RC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (08) :3539-3543
[7]   Dendritic cells in cancer immunotherapy [J].
Fong, L ;
Engleman, EG .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :245-273
[8]  
Gabrilovich DI, 1999, CLIN CANCER RES, V5, P2963
[9]   Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells [J].
Gong, JL ;
Chen, DS ;
Kashiwaba, M ;
Kufe, D .
NATURE MEDICINE, 1997, 3 (05) :558-561
[10]   Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells [J].
Gong, JL ;
Avigan, D ;
Chen, DS ;
Wu, ZK ;
Koido, S ;
Kashiwaba, M ;
Kufe, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (06) :2715-2718