難治性固形癌に対する癌抗原ペプチドパルス樹状細胞を用いた癌ワクチン療法 : トランスレーショナルリサーチとしての展開
スポンサーリンク
概要
- 論文の詳細を見る
Dendritic cells (DCs) are the most potent antigen-presenting cells. DCs pulsed withpeptides of tumor-associated antigens (TAA) have been used in cancer immunotherapy. Anearly clinical study demonstrated the safety of these trials, but the clinical effect was notsufficient. Most studies have used immature DCs generated from peripheral bloodmonocytes 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 DCsinduced by a streptococcus derivatives OK-432. DCs were generated from bloodmonocytes 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 controlantigen. We selected HLA-A*2402-positive patients who had advanced solid tumorsexpressing MAGE-3 mRNA. DC vaccine was administered subcutaneously every 2 weeksfor 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 withdelayed type hypersensitivity (DTH) reaction and MHC tetramer was performed. Threepatients with advanced solid tumor (two lung cancer and one melanoma patients) were sofar enrolled in Group 1 of this study. This protocol was well tolerated. A mild fever (Grade 1to 2) and local reaction of injection site (erythema and induration : Grade 1) were found in allpatients. DTH for MAGE-3 peptide became to be positive after forth vaccination in onepatient. The decrease of tumor marker (CEA) was found in one patient. However, clinicalresponses in all three patients were not observed. These results indicated that vaccinationwith mature DCs (0.1×10８DCs/injection) was safe and feasible, but further analysis usingthe higher dose of DCs was required to assess the immunological and clinical responses.
- 徳島医学会の論文
- 2003-12-25
徳島医学会 | 論文
- 後天性QT延長症候群の病態 (特集1:心臓突然死を考える)
- がん治療薬と副作用 (特集 がんと栄養)
- 症例報告 合成吸収性癒着防止材を使用した胃全摘術後に発症した絞扼性イレウスの一例
- ヒト肺癌培養細胞株の樹立とその生物学的性状
- 症例報告 肝嚢胞性腫瘍の2切除例