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進行肺癌に対する術前・術後養子免疫療法に関する基礎的並びに臨床的研究
https://doi.org/10.24517/00067205
https://doi.org/10.24517/00067205359f38ff-20cf-45e7-a0ee-d4d709df0e6d
| 名前 / ファイル | ライセンス | アクション |
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ME-PR-WATANABE-Y-kaken 1993-3p.pdf (123.7 kB)
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| Item type | 報告書 / Research Paper(1) | |||||
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| 公開日 | 2022-11-25 | |||||
| タイトル | ||||||
| タイトル | 進行肺癌に対する術前・術後養子免疫療法に関する基礎的並びに臨床的研究 | |||||
| タイトル | ||||||
| タイトル | Study on Adoptive Immuno-therapy for Advanced Lung Cancer. | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
| 資源タイプ | research report | |||||
| ID登録 | ||||||
| ID登録 | 10.24517/00067205 | |||||
| ID登録タイプ | JaLC | |||||
| 著者 |
渡辺, 洋宇
× 渡辺, 洋宇 |
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| 提供者所属 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 金沢大学医学部 | |||||
| 書誌情報 |
平成1(1989)年度 科学研究費補助金 一般研究(C) 研究成果報告書概要 en : 1989 Fiscal Year Final Research Report Summary 巻 1989 – 1990, p. 3p., 発行日 1993-08-11 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 進行肺癌に対する補助療法としての養子免疫療法に関する基礎的ならびに臨床的研究を行った。(1)末梢血リンパ球(PBL)、領域リンパ節リンパ球(RLNL)および腫瘍内浸潤リンパ球(TIL)について、抗腫瘍活性の賦活法について検討した。RLNLおよびTILのNK(Natural Killer)活性は、PBLに比べその活性は有意に低かった。一方、肺癌患者のPBLのILー2産生能は対照群(健康人PBL)と比較して有意に低下しているが、肺癌患者の転移のない領域リンパ節からえたRLNLのILー2産生能は、PBLに比べて有意に亢進していることがわかった。肺癌患者のPBL、転移リンパ節RLNL、非転移リンパ節RLNLおよび切除肺の腫瘍内TILをrILー2と5日間培養すると、細胞傷害活性は著しく増強された。これはLAK細胞の誘導によるものであり、TIL、RLNL、PBLで比較すると、PBLで誘導されるLAK活性が最も高い活性を示した。またこれらPBLーLAK細胞の自己腫瘍細胞に対する細胞傷害活性は、rILー2にマイトマイシン処理した自己腫瘍細胞を添加して培養した場合が最も高く賦活された。モノクロナ-ル抗体を用いてのリンパ球亜群を検索した結果、PBLーLAKの大部分はNK細胞期限であるのに対し、RLNLおよびTILから誘導されるLAK細胞の起源の大部分は(一部はNK細胞由来であっても)細胞傷害性T細胞であることが明らかになった。(2)肺癌患者のPBLを高密度自動細胞培養装置にてrILー2を添加、2〜3週間培養し、回収されたPBLーLAK細胞を患者の気管支動脈内に再注入した。その結果、7例中、PR2例、MR3例と5例に何らかの効果がえられ、2例はNCであった。また癌性胸膜炎患者の胸水より分離したTILをrILー2添加のもとに高密度自動細胞培養装置にて培養し、患者の胸腔内に戻す養子免疫療法を3例に施行し、2例に胸水の消失をみとめた。 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | It appears that lymph node metastases are more frequent in lung cancer than in other cancers due to impaired defensive mechanisms in the regional lymph nodes. However, little is known about the immunological function of Regional Lymph Node Lymphocytes (RLNL) in lung cancer patients. We have studied the immunological properties of RLNL in comparison with Peripheral Blood Lymphocytes (PBL). We measured the Natural Killer (NK) cell activity of RLNL and PBL in lung cancer patients and found that the NK activity was significantly more depressed in the RLNL than in the PBL. In contrast, Inter-Leukin-2 (IL-2) production was markedly higher in the RLNL than in the PBL. The cytotoxic effect of RLNL in non-metastatic lymph nodes on target cells, such as K562 cells, or PC-3 and PC-10 cells (NK-resistant, human lung cancer of adenocarcinoma and epidermoid carcinoma, respectively) was significantly enhanced by in vitro incubation with recombinant IL-2 (rIL-2). Furthermore, we clarified that both rIL-2 and OK-432, which is a biological response modifier and IL-2 inducer as well, augmented the cytotoxicity of RLNL and that these effector cells were lymphokine activated killer (LAK) celis. The depletion of lymphocyte subsets by pretreatment with specific monoclonal antibody showed that the LAK activity in RLNL was mediated by CD3^+ and CD8^+ cells, while the lymphocyte subsets contributing the LAK activity in PBL were CD3^+ and CD16^+ cells. It was concluded that a majority of the effector cells in RLNL were LAK cells of the cytotoxic T-cell population. Thus, therapeutic effects can be expected by LAK cells endogenously induced by regional infusion of OK-432 abd addition of exogenous LAK cells which can be produced in vitro by incubating the patient's lymphocytes with rIL-2. Local AIT through bronchial artery was performed on 7 patients with advanced lung cancer. Some therapeutic effects were noted in 5 (71%) out of 7 patients : partial response in 2, minor response in 3 and no change in 2. As the next step, possibility of adpotive immunotherapy using TIL (Tumor Infiltrating Lymphocyte) was studied Substantial augmentation of the cytotoxic activity against K562, Daudi and autologous tumor cell lines were induced by incubating the TILs with OK-432 or rIL-2, although these enhancement of the cytotoxicity was significantily low in comparison with that of the RLNLs and PBLs. By analysis of lymphocyte subsets, it was clarified that the majority of the TILs were T cells (most of them were CD8^+ cells), whereas B cells, macrophages and NK cells were minority. These tesults strongly indicates that, if not all, some part of cultured TIL contains cytotoxic T lymphocytes which have a specificity against autologous tumor cells. Accordingly, it was thought to be probable that some of the cytotoxic T cells (CTLs) in the TILs might have cytotoxicty against AT cells. Adoptive Immuno-Therapy (AIT) was tried on lung cancer patients with carcinomatous pleurosy. TILs were extracted from pleural effusion, and enhanced by rIL-2. The enhanced TILs with rIL-2 were infused into the thoracic cavity, and subsequently in two out of three cases the pleural effusion disappeared. |
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| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 研究課題/領域番号:01570779, 研究期間(年度):1989 – 1990 | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 出典：研究課題「進行肺癌に対する術前・術後養子免疫療法に関する基礎的並びに臨床的研究」課題番号01570779 （KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-01570779/015707791990kenkyu_seika_hokoku_gaiyo/）を加工して作成 |
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| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| 関連URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://kaken.nii.ac.jp/search/?qm=20019897 | |||||
| 関連名称 | https://kaken.nii.ac.jp/search/?qm=20019897 | |||||
| 関連URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-01570779/ | |||||
| 関連名称 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-01570779/ | |||||
| 関連URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-01570779/015707791990kenkyu_seika_hokoku_gaiyo/ | |||||
| 関連名称 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-01570779/015707791990kenkyu_seika_hokoku_gaiyo/ | |||||
