ID 39620
Title Transcription
ナンジセイ コケイガン ニ タイスル ガン コウゲン ペプチドパルス ジュジョウ サイボウ オ モチイタ ガン ワクチン リョウホウ : トランスレーショナル リサーチ トシテノ テンカイ
Title Alternative
Vaccination of lung cancer patients with dendritic cells pulsed with tumor antigen peptides
Author
Nishioka, Yasuhiko Department of Internal Medicine and Molecular Therapeutics, Course of Medical Oncology, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Nakagawa, Tatsuo Clinical Trial Center for Developmental Therapeutics, Tokushima UniversityHospital
Sone, Saburo Department of Internal Medicine and Molecular Therapeutics, Course of Medical Oncology, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
dendritic cells
MAGE-3
mature DCs
OK-432
HLA-A*2402
Content Type
Journal Article
Description
Dendritic cells (DCs) are the most potent antigen-presenting cells. DCs pulsed with peptides of tumor-associated antigens (TAA) have been used in cancer immunotherapy. An early clinical study demonstrated the safety of these trials, but the clinical effect was not sufficient. Most studies have used immature DCs generated from peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Here, we conducted phase I clinical trial of active immunotherapy using mature DCs induced by a streptococcus derivatives OK-432. DCs were generated from blood monocytes by culturing with GM-CSF and IL-4 for 6 days and then GM-CSF, IL-4 and OK-432 for 2 days. Before injection, DCs were pulsed with MAGE-3 peptide (IMPKAGLLI), which is restricted for HLA-A*2402, and keyhole limpet hemocyanin (KLH) as a control antigen. We selected HLA-A*2402-positive patients who had advanced solid tumors expressing MAGE-3 mRNA. DC vaccine was administered subcutaneously every 2 weeks for a total of four vaccinations in a dose-escalation design at the dose level per cohort of 0.1 (Group 1), 0.3 (Group 2) and 1 (Group 3) ×108DCs/injection. Immunological monitoring with delayed type hypersensitivity (DTH) reaction and MHC tetramer was performed. Three patients with advanced solid tumor (two lung cancer and one melanoma patients) were so far enrolled in Group 1 of this study. This protocol was well tolerated. A mild fever (Grade 1 to 2) and local reaction of injection site (erythema and induration : Grade 1) were found in all patients. DTH for MAGE-3 peptide became to be positive after forth vaccination in one patient. The decrease of tumor marker (CEA) was found in one patient. However, clinical responses in all three patients were not observed. These results indicated that vaccination with mature DCs (0.1×108DCs/injection) was safe and feasible, but further analysis using the higher dose of DCs was required to assess the immunological and clinical responses.
Journal Title
四国医学雑誌
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
59
Issue
6
Start Page
280
End Page
286
Sort Key
280
Published Date
2003-12-25
Remark
EDB ID
FullText File
language
jpn
departments
Medical Sciences