ID 39620
タイトルヨミ
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
タイトル別表記
Vaccination of lung cancer patients with dendritic cells pulsed with tumor antigen peptides
著者
西岡, 安彦 徳島大学医学部生体防御腫瘍医学講座分子制御内科学分野 徳島大学 教育研究者総覧 KAKEN研究者をさがす
中川, 達夫 徳島大学病院臨床試験管理センター
曽根, 三郎 徳島大学医学部生体防御腫瘍医学講座分子制御内科学分野 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
dendritic cells
MAGE-3
mature DCs
OK-432
HLA-A*2402
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
四国医学雑誌
ISSN
00373699
cat書誌ID
AN00102041
出版者
徳島医学会
59
6
開始ページ
280
終了ページ
286
並び順
280
発行日
2003-12-25
備考
EDB ID
フルテキストファイル
言語
jpn
部局
医学系