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PMID: 14520441 Published · ppublish English Clinical Trial Clinical Trial, Phase I Clinical Trial, Phase II Journal Article

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

British journal of cancer ·Vol. 89 ·No. 7 ·2003-10-06 ·Pages 1172-9

Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T, Narita M, Takahashi M, Tanaka R

Abstract

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.

MeSH Terms
Adult Aged Antigens, CD/metabolism Brain Neoplasms/immunology,prevention & control,therapy Cancer Vaccines/administration & dosage Cytokines/metabolism Dendritic Cells/immunology,transplantation Female Glioma/immunology,prevention & control,therapy Humans Hypersensitivity, Delayed/etiology Immunoenzyme Techniques Immunotherapy Lymphocytes, Tumor-Infiltrating/immunology Male Middle Aged T-Lymphocytes, Cytotoxic/immunology Tumor Cells, Cultured Vaccination
Chemicals
Antigens, CD Cancer Vaccines Cytokines
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Yamanaka R
Department of Neurosurgery, Brain Research Institute, Niigata University, Asahimachi-dori 1-757, Niigata City, 951-8585, Japan. [email protected]
Abe T
Yajima N
Tsuchiya N
Homma J
Kobayashi T
Narita M
Takahashi M
Tanaka R
References (33)
33 references, click to expand
  1. Differential expression of transforming growth factor-beta 1, -beta 2, and -beta 3 by glioblastoma cells, astrocytes, and microglia.
    J Immunol. 1992 Mar 1;148(5):1404-10 PMID: 1538124
  2. Response criteria for phase II studies of supratentorial malignant glioma.
    J Clin Oncol. 1990 Jul;8(7):1277-80 PMID: 2358840
  3. Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo.
    J Exp Med. 1993 Aug 1;178(2):479-88 PMID: 7688024
  4. Production of IL-10 by melanoma cells: examination of its role in immunosuppression mediated by melanoma.
    Int J Cancer. 1994 Mar 1;56(5):755-60 PMID: 8314354
  5. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity.
    Nat Med. 1995 Dec;1(12):1297-302 PMID: 7489412
  6. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells.
    Nat Med. 1996 Jan;2(1):52-8 PMID: 8564842
  7. T-cell costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are expressed in human microglia but not in astrocytes in culture.
    Brain Res. 1995 Dec 15;704(1):92-6 PMID: 8750966
  8. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
    J Exp Med. 1996 Aug 1;184(2):465-72 PMID: 8760800
  9. Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.
    Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10399-404 PMID: 8816812
  10. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells.
    Nat Med. 1997 May;3(5):558-61 PMID: 9142127
  11. Dendritic cells in the T-cell areas of lymphoid organs.
    Immunol Rev. 1997 Apr;156:25-37 PMID: 9176697
  12. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.
    Nat Med. 1998 Mar;4(3):328-32 PMID: 9500607
  13. Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides.
    Prostate. 1998 Jun 15;36(1):39-44 PMID: 9650914
  14. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens.
    J Neurosurg. 1999 Jun;90(6):1115-24 PMID: 10350260
  15. Induction of systemic and therapeutic antitumor immunity using intratumoral injection of dendritic cells genetically modified to express interleukin 12.
    Cancer Res. 1999 Aug 15;59(16):4035-41 PMID: 10463604
  16. Treatment of a patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I-matched tumor peptides. Case Report.
    Neurosurg Focus. 2000;9(6):e8 PMID: 16817691
  17. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye.
    Br J Exp Pathol. 1948 Feb;29(1):58-69 PMID: 18865105
  18. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function.
    Clin Cancer Res. 1999 Oct;5(10):2963-70 PMID: 10537366
  19. Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma.
    J Neuroimmunol. 2000 Feb 1;103(1):16-25 PMID: 10674985
  20. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.
    Nat Med. 2000 Mar;6(3):332-6 PMID: 10700237
  21. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells.
    Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2715-8 PMID: 10688917
  22. Dendritic cells in cancer immunotherapy.
    Annu Rev Immunol. 2000;18:245-73 PMID: 10837059
  23. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration.
    Cancer Res. 2001 Feb 1;61(3):842-7 PMID: 11221866
  24. Enhancement of antitumor immune response in glioma models in mice by genetically modified dendritic cells pulsed with Semliki forest virus-mediated complementary DNA.
    J Neurosurg. 2001 Mar;94(3):474-81 PMID: 11235953
  25. Antitumor effect of immunizations with fusions of dendritic and glioma cells in a mouse brain tumor model.
    J Immunother. 2001 Mar-Apr;24(2):106-13 PMID: 11265767
  26. Immunization with dendritic cells pulsed with tumor extract increases survival of mice bearing intracranial gliomas.
    J Neurooncol. 2001 Jan;51(1):1-9 PMID: 11349874
  27. Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells.
    Cancer Immunol Immunother. 2001 Sep;50(7):337-44 PMID: 11676393
  28. Dendritic cells pulsed with tumor extract-cationic liposome complex increase the induction of cytotoxic T lymphocytes in mouse brain tumor.
    Cancer Immunol Immunother. 2001 Nov;50(9):463-8 PMID: 11761440
  29. A dendritic cell vaccine induces protective immunity to intracranial growth of glioma.
    Anticancer Res. 2002 Mar-Apr;22(2A):613-21 PMID: 12014629
  30. 7-Hydroxystaurosporine-induced apoptosis in 9L glioma cells provides an effective antigen source for dendritic cells and yields a potent vaccine strategy in an intracranial glioma model.
    Neurosurgery. 2002 Jun;50(6):1327-34; discussion 1334-5 PMID: 12015852
  31. Administration of interleukin-12 and -18 enhancing the antitumor immunity of genetically modified dendritic cells that had been pulsed with Semliki forest virus-mediated tumor complementary DNA.
    J Neurosurg. 2002 Nov;97(5):1184-90 PMID: 12450042
  32. Dendritic cell-based glioma immunotherapy (review).
    Int J Oncol. 2003 Jul;23(1):5-15 PMID: 12792771
  33. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3539-43 PMID: 8097319
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
Published
2003-10-06
Pages
1172-9
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2394324
Subset
IM
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