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病理組織学的に神経膠腫グレード3または4(膠芽腫)と診断され,かつ術後,かつ放射線治療あるいは放射線化学療法のいずれかを施行するも無効,または再発した患者を対象として,テーラーメイドペプチドワクチンを投与し,その安全性,免疫反応性,臨床効果を検討した2つの臨床研究について以下にまとめた。
登録された全症例は27例であり,ワクチン投与は,隔週1回,3mgペプチドを投与する群(隔週投与群)と,毎週1回,2mgペプチドを投与する群(毎週投与群)の2つのプロトコールを設定した。各々のプロトコールにおいて,6回投与後のペプチドに対する特異的免疫反応性の解析を行った。臨床的に好ましい効果が得られた場合は,被験者の同意を再度得てから同ペプチドワクチンの継続投与を行い,全投与期間における毒性の評価と,RECIST(response evaluation criteria in solid tumors:MRIまたはCT画像における1方向測定法)による臨床効果(腫瘍縮小)の検討も行った。非無作為に実施された臨床研究であり,隔週投与群13例,毎週投与群14例の計27症例が登録された。隔週投与群では13例中女性が9人,毎週投与群14例中では男性が13人であった。今回の治験対象となるHLA-A24の膠芽腫症例は,隔週投与で8例,毎週投与で6例の合計14例と,登録された膠芽腫18症例のうち大多数を占めた1)。
Purpose:The primary goal of this phaseⅠ study was to assess the safety and immunological responses of personalized peptide vaccination for patients with advanced malignant glioma.
Experimental Design:Twenty-five patients with advanced malignant glioma(8 grade 3 and 17 grade 4 gliomas)were evaluated in a phaseⅠ clinical study of a personalized peptide vaccination. For personalized peptide vaccination, pre-vaccination peripheral blood mononuclear cells and plasma were provided to examine cellular and humoral responses to 25 or 23 peptides in HLA-A24+ or HLA-A2+ patients, respectively, and then only the reactive peptides(maximum:4)were used for in vivo administration.
Results:The protocols were well tolerated with local redness and swelling at the injection site in most cases. Twenty-one patients received more than six vaccinations and were evaluated for both immunological and clinical responses. Increases in cellular or humoral responses specific to at least one of the vaccinated peptides was observed in the post-vaccination(6th)-samples from 14 or 11 of 21 patients, respectively. More importantly, significant levels of peptide-specific IgG were detected in the post-vaccination tumor cavity or spinal fluid of all of the tested patients who showed favorable clinical responses. Clinical responses were 5 partial responses, 8 cases of stable disease, and 8 cases of progressive disease. The median overall survival for patients with recurrent glioblastoma multiforme in this study(n=17)was 622 days.
Conclusions:Personalized peptide vaccinations were recommended for the further clinical study to malignant glioma patients.
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