記事→10月4日の「ＰＲ情報」で、『ブライトパスの共同研究先である 国立研究開発法人国立がん研究センター先端医療開発センター医薬品開発部グループ免疫療法開発分野長 中面哲也氏が、個別化ネオアンチゲンワクチン療法（演題：Personalized peptide vaccine）について、2019年10月11ｰ13日までの期間タイで開催されるASCO Breakthrough 2019で発表されます。』と紹介されていました。
中面先生は、残念ながら台風１９号の影響でタイへ渡航できなかったようですが、東京とタイの会場を生放送で繋いで、口演は行われたようです。その口演内容をASCOがアップしています。⇒
https://meetinglibrary.asco.org/record/180793/video
口演（26枚のスライドで約10分間）を視聴すると、後半の今後の計画の件（くだり）で「ブライトパスバイオ」という固有名詞が二度出てきます（頼もしい限りです。太字参照）。
ビデオで聞き取りやすい中面さんの英語を是非視聴してみてください。ビデオ画面の右下に中面先生の顔が終始映し出されています。
以下に口演内容を和訳してみました。拙い訳ですが参考にしてください。
和訳⇒
司会者：まず最初は、東京の中面先生です。彼は東京の国立がんセンター病院の博士です。残念ながら台風の影響でこの場には参加されていませんが、彼はご無事です。今日は、ズームを介してこの講演会に参加されます。Gritstone OncologyのDr. Andrew Allenがこちらにいらっしゃいますので、ペプチドベースの個別ワクチンと個別化された癌ワクチンの両方について、彼らから詳しくお話を聞きましょう。
司会者：よろしいでしょうか？中面先生？
中面：ええ、ありがとうございます。
司会者：それではよろしくお願いします。
中面：OK。ありがとう、ヨハンナさん。
中面：今日の講演のタイトルは、ペプチドベースの個別化ワクチンです。最初に、共有抗原グリピカン-3を使用した実験を紹介します。次に、個別化ワクチンの計画を示します。グリピカン-3は癌胎児性抗原です。そして、共有抗原は、肝細胞癌に対する抗癌免疫療法の理想的な標的です。グリピカン-3は、肝細胞癌の80％で過剰発現しています。そして、正常な器官では発現はありません。そして、胎盤と胎児の肝臓と胎児の腎臓でメッセンジャーRNAレベルとタンパク質レベルで発現しています。
肝細胞癌患者の30％がグリピカン3陰性を示しています。そして、彼らは良い予後を示しています。グリピカン-3は、肝細胞癌患者の80％の予後不良です。 10年生存率はわずか20％です。
したがって、このスライドは、ペプチドワクチン療法のメカニズムの概要を示しています。皮内または皮下にアジュバントを注入してペプチドを注入しました。ペプチドは皮膚の樹状細胞にロードされます。そしてリンパ節では、CTLがある場合、この受容体はHLAクラスIおよびペプチド複合体を認識できます。そして、これらのCTLは、HLAクラスIのこのペプチドで癌細胞を拡大および増加させて攻撃しますが、正常細胞を攻撃しません。
そこで、グリピカン-3ペプチドを使用した第I相臨床試験を完了しました。皆さんご存知の通り、HLA-A2は白人の一般的なHLAです。日本人の40％がHLA-A2を保有しています。また、日本人の60％がHLA-A24を持っています。これらの2種類のペプチドがペプチド特異的CTLを誘導できることを確認しました。
また、現在の臨床試験では、33人の患者で1つの部分奏効を経験しました。したがって、これらの患者では、3回目のワクチン接種後に腫瘍が縮小します。そして、この腫瘍は壊死を示します。これらの2つの腫瘍は消えます。そして、同じサイズの肝臓に腫瘍があります。インフォームドコンセントの後、生検を行いました。驚くべきことに、我々はCD8陽性T細胞を検出しました。多くの、変化した腫瘍にCD8陽性T細胞があります。
そしてこのスライドは、これは別の患者、進行肝細胞癌患者です。多くの肝細胞がんがあります。そして、2回のペプチドワクチン接種後のみ、ほとんどすべての腫瘍が壊死を示しました。しかし、残念なことに、彼は右心房の腫瘍血栓のために死亡しました。
これはデータです。顕微鏡的に、これらの肝細胞癌腫瘍は壊死を示しました。そして病理学的には、すべての腫瘍が中心壊死を示しました。そして、腫瘍を取り囲む多くのCD8陽性T細胞があります。
また、卵巣明細胞癌では、グリピカン-3の発現も示されました。この患者では、多くの種類の化学療法が失敗しました。そしてその後、ペプチドワクチン接種が腫瘍に注入されました。これらの腫瘍マーカーの2種類は、ペプチドワクチン接種のみで減少しました。この患者には、卵巣明細胞がんで腫瘍転移があります。そして、この患者は部分奏効を示しました。
この進行がんでは、部分奏効または完全奏効などの臨床反応を示した患者は3〜5％のみです。したがって、次の研究は、注射または大規模な治療後のアジュバント設定研究です。そのため、治療スケジュールは、根治手術後1年で10回の予防接種です。
すでにこのデータは公開しています。1年の再発率は24％で、対照群は50％です。グリピカン-3ペプチドワクチンは再発を防ぐ可能性があります。
これが全体的な生存データです。したがって、グリピカン-3陰性は予後良好な要因です。グリピカン-3陰性患者は、ペプチドワクチン接種または手術のみではなく、良好な予後を示しました。しかし、グリピカン-3陽性患者はペプチドワクチンなしでは予後不良を示しました。ペプチドワクチン群はワクチン接種後に良好な予後を示しました。
私はすでに小児がんのデータフェーズI臨床試験を発表しました。したがって、この試験では、肝芽腫の5人の患者寛解グループが登録されました。そして、すべての肝芽腫患者は再発せず、良好な生存率を示しました。
これはペプチド特異的CTLのモニタリングの代表的なデータです。このデータは、エクスビボでのインターフェロンガンマに由来します。そして、このデータは、グリピカン-3クラスIを使用したフローサイトメトリーデータです。この患者では、ペプチド特異的CTLはありません。
この集団をソートすることにより、特定のCTLクローンを簡単にペプチド化できました。そして、これらのCTLクローンは高い能力と高い特異性を示しました。そして、彼らはグリピカン-3陽性のがん細胞のみを攻撃することができます。そのため、ペプチドワクチンはペプチド特異的CTLを誘導できます。そして、このT細胞受容体は、形質導入されたT細胞血清に有用です。また、グリピカン-3も膜タンパク質です。したがって、抗体療法またはCAR T細胞療法は、標的化グリピカン-3療法に有用です。
次に、日本企業のBrightPath Bioとの共同研究で、個別化ペプチドワクチンの計画についてお話しします。これは、開発中のネオアンチゲンを標的とした免疫療法のデータです。これは、共有抗原とネオアンチゲンです。そして、これがペプチドワクチンまたはワクチンなどです。
これは特定の臨床試験における臨床研究または治験責任医師(病院)のリストです。多くの種類の試験が米国とヨーロッパと中国で進行中です。また、とても多くの種類のペプチドワクチンの臨床試験が進行中です。そしてこのスライドは、多くの企業が臨床試験を後援したことを示しています。そこでは、多くの臨床試験が進行中です。
これはNature 2017で公開された有名な図です。このグループは、進行性黒色腫患者を対象とした良好な臨床反応を示しました。これは再発防止設定です。そのため、これはアジュバントとして長いペプチドワクチンとポリICLCを使用しています。
これは、オランダのグループバイオテクノロジーグループから派生した有名なデータです。この研究はRNAワクチンを使用しており、同様の状況で標的化された進行性黒色腫を有し、再発を防止します。
このスライドはペプチドワクチンのリファレンスを示しています。短いペプチドを使用します。そして、日本企業のBrightPath Bioとの共同研究では、長いペプチドとpoly-ICLCを使用することを計画しています。これは間近です。そして、私はこのスライドでそれを示します。
次に、日本企業のBrightPath Bioとの共同研究で、個別化ペプチドワクチンの計画についてお話しします。これは、開発中のネオアンチゲンを標的とした免疫療法のデータです。これは、共有抗原とネオアンチゲンです。そして、これがペプチドワクチンまたはワクチンなどです。
これは特定の臨床試験における臨床研究または治験責任医師(病院)のリストです。多くの種類の試験が米国とヨーロッパと中国で進行中です。また、とても多くの種類のペプチドワクチンの臨床試験が進行中です。そしてこのスライドは、多くの企業が臨床試験を後援したことを示しています。そこでは、多くの臨床試験が進行中です。
これはNature 2017で公開された有名な図です。このグループは、進行性黒色腫患者を対象とした良好な臨床反応を示しました。これは再発防止設定です。そのため、これはアジュバントとして長いペプチドワクチンとポリICLCを使用しています。
これは、オランダのグループバイオテクノロジーグループから派生した有名なデータです。この研究はRNAワクチンを使用しており、同様の状況で標的化された進行性黒色腫を有し、再発を防止します。
このスライドはペプチドワクチンのリファレンスを示しています。短いペプチドを使用します。そして、日本企業のBrightPath Bioとの共同研究では、長いペプチドとpoly-ICLCを使用することを計画しています。これは間近です。そして、私はこのスライドでそれを示します。
これは、ネオアンチゲンを識別するためのワークフローです。そしてこれは、高度な免疫原性エピトープの細胞内プロセシングを伴うHLA 発現と提示です。 in vitroおよびin vivoで免疫原性エピトープを選択します。そのため、乳癌と血液癌およびネオアジュバント化学療法群を対象とする計画があります。したがって、乳癌と血液癌のネオアジュバント化学療法の後、化学療法に対処するために、長鎖のペプチドを選択し、数種類のペプチドとワクチン接種を行います。
これは要約、結論のスライドです。
これは要約、結論のスライドです。
・ネオアンチゲンを標的とする免疫療法が開発され、
・個人の免疫腫瘍学療法に関する多くの臨床研究が進行中です。
・また、日本企業と協力して、ペプチドベースの個別ワクチンの臨床試験を計画しています。
どうもありがとうございました。
以上です。
因みに最後の結論(Conclusions)の部分の原文は以下の通りです。
Conclusions /Take.Away
・Immunotherapies targeting neoantigens were developed .
・Many Clinical Studies for Personalized Immuno-oncology Therapies is ongoing.
・We are also planning a clinical traial of peptide-based individualized vaccines in cooperation with Japanese company.
最後のセンテンスの「with Japanese company」とは、もちろんブライトパスのことです。
これまでの治験で使っていた短鎖ペプチドではなく、ハードルの高い長鎖ペプチドを用いて、まずは肺がんと血液がんでの治験を計画中とのことです。
完全個別化ネオアンチゲン療法は、極めて難易度の高いチャレンジですが、最も注目を集めている免疫療法であり、がん免疫治療を主戦場と定めているブライトパスはこれを避けては前に進めません。
途中経過でも、着実な前進をこのような形で情報発信してもらうと、投資家も会社の方向性を再確認することが出来て、中長期的な投資マインドが維持することができます。
情報の修正を提案
翻訳の共有
送信
キャンセル
修正していただいた翻訳は、翻訳の品質向上に活用させていただきます。このため、修正内容を他のユーザーに公開する場合があります（修正したユーザーが特定されることはありません）
もう一度お試しください
ご協力いただき、ありがとうございました
修正していただいた翻訳は、翻訳の品質向上に活用させていただきます
詳細
00:00 First colleague, Dr. Nakatsura from Tokyo. He's from National Cancer Center Hospital in Tokyo. He was unable to join us because of the typhoon. But he is safe and sound, and will be joining us via Zoom. And then we have Dr. Andrew Allen from Gritstone Oncology. So we're excited to hear a little bit more about from them about both peptide-based individual vaccines as well as personalized cancer vaccines. 00:30 So I think we're getting in touch with-- 00:32 Thank you. 00:32 There we go. Dr. Nakatsura? 00:35 Yeah, thank you. 00:36 Please take it away. 00:38 OK. Thank you, Johanna. 00:40 Thank you. 00:42 The title of today's talk is peptide-based individualized vaccines. At first I will show you the experiments using shared antigen glypican-3. And next I will show the plan of individualized vaccines. Glypican-3 is a carcinoembryonic antigen. And the shared antigen is the ideal target of anticancer immunotherapy against hepatocellular carcinoma. Glypican-3 is overexpressed in 80% of hepatocellular carcinoma. And in normal organs there is no expression. And there's expression at the placenta and fetal liver and fetal kidney at the messenger RNA level and protein level. 01:36 30% of hepatocellular carcinoma patient shows a glypican-3 negative. And they show the good prognosis. The glypican-3 is a bad prognosis of the 80% of hepatocellular carcinoma patient. 10 year survival rate is only 20%. 02:00 So this slide shows the outline of the mechanism of [INAUDIBLE] of peptide vaccine therapy. We injected the peptide with adjuvant injected intradermally or subcutaneously. The peptide is loaded on the dendritic cells at the skin. And at the lymph node, if there is a CTL have this receptor can recognize HLA class I and peptide complexes. And these CTL expand and increased and attack the cancer cells with this peptide on the HLA class I, but do not attack the normal cells. 02:56 So we completed the phase I clinical trial using glypican-3 peptide. So as you know, HLA-A2 is a common HLA in the Caucasian. 40% of Japanese has HLA-A2. And HLA-A24 is a measure in Japan. So 60% of Japanese have HLA-A24. We identified these kind of two peptides can induce peptide-specific CTLs. 03:29 And in present clinical trial, we experienced one partial response cases in the 33 patients. So in these patients, after only third vaccination there's tumor shrinkage. And this tumor shows necrosis. These two tumors are disappeared. And there is a tumor on the liver of the same size. And after informed consent, we did the biopsy. So surprisingly, we detected the [INAUDIBLE] the CD8 positive T cells-- many, many CD8 positive T cells in the changed tumor. 04:22 So this is another patient, advanced hepatocellular carcinoma patient. So there is many hepatocellular carcinoma. And only after two peptide vaccinations, almost all tumors showed necrosis. But unfortunately, he died because of tumor thrombus at the right atrium. 04:50 This is data. Microscopically, these hepatocellular carcinoma tumor showed necrosis. And in pathologically, all the tumor showed central necrosis. And there is many CD8 positive T cells surrounding the tumor. 05:15 So in ovarian clear cell carcinoma, also showed glypican-3 expression. So in this patient, many kind of chemotherapy failed. And after that, peptide vaccination injected into the tumor. So two kinds of these tumor markers decreased after only peptide vaccination. In this patient there is a [INAUDIBLE] tumor metastasis of ovarian clear cell carcinoma. And they showed [INAUDIBLE] were enlarged and disappeared. This patients showed the partial response. 06:00 So in this advanced cancer only 3% to 5% patients showed clinical response, like partial response or complete response. So next study is adjuvant setting study after injection or larger [INAUDIBLE] treatment. So the treatment schedule is 10 times vaccination in a year after curative operation. 06:38 So we already published this data. So one year recurrence rate of 24% and control group is 50%. So glypican-3 peptide vaccine may prevent recurrence. 06:59 So this is a data, the overall survival data. So glypican-3 negative is a good prognosis factor. So glypican-3 negative patient showed good prognosis instead of peptide vaccination or surgery only. But glypican-3 positive patient showed bad prognosis without peptide vaccine. But peptide vaccine group showed good prognosis after vaccination. 07:34 So I already published the data phase I clinical trial of the pediatric cancer. So in this trial, five patients remission group of hepatoblastoma enrolled. So all hepatoblastoma patients showed without recurrence and good survival. 08:08 So this is a representative data of monitoring of peptide specific CTLs. This data is derived from interferon-gamma ex vivo [INAUDIBLE]. And this data is flow cytometry data using glypican-3 class I [INAUDIBLE]. So in this patient there is no peptide specific CTLs before pe
「00:00 First colleague, Dr. Nakatsura from Tokyo. He's from National Cancer Center Hospital in Tokyo. He was unable to join us because of the typhoon. But he is safe and sound, and will be joining us via Zoom. And then we have Dr. Andrew Allen from Gritstone Oncology. So we're excited to hear a little bit more about from them about both peptide-based individual vaccines as well as personalized cancer vaccines. 00:30 So I think we're getting in touch with-- 00:32 Thank you. 00:32 There we go. Dr. Nakatsura? 00:35 Yeah, thank you. 00:36 Please take it away. 00:38 OK. Thank you, Johanna. 00:40 Thank you. 00:42 The title of today's talk is peptide-based individualized vaccines. At first I will show you the experiments using shared antigen glypican-3. And next I will show the plan of individualized vaccines. Glypican-3 is a carcinoembryonic antigen. And the shared antigen is the ideal target of anticancer immunotherapy against hepatocellular carcinoma. Glypican-3 is overexpressed in 80% of hepatocellular carcinoma. And in normal organs there is no expression. And there's expression at the placenta and fetal liver and fetal kidney at the messenger RNA level and protein level. 01:36 30% of hepatocellular carcinoma patient shows a glypican-3 negative. And they show the good prognosis. The glypican-3 is a bad prognosis of the 80% of hepatocellular carcinoma patient. 10 year survival rate is only 20%. 02:00 So this slide shows the outline of the mechanism of [INAUDIBLE] of peptide vaccine therapy. We injected the peptide with adjuvant injected intradermally or subcutaneously. The peptide is loaded on the dendritic cells at the skin. And at the lymph node, if there is a CTL have this receptor can recognize HLA class I and peptide complexes. And these CTL expand and increased and attack the cancer cells with this peptide on the HLA class I, but do not attack the normal cells. 02:56 So we completed the phase I clinical trial using glypican-3 peptide. So as you know, HLA-A2 is a common HLA in the Caucasian. 40% of Japanese has HLA-A2. And HLA-A24 is a measure in Japan. So 60% of Japanese have HLA-A24. We identified these kind of two peptides can induce peptide-specific CTLs. 03:29 And in present clinical trial, we experienced one partial response cases in the 33 patients. So in these patients, after only third vaccination there's tumor shrinkage. And this tumor shows necrosis. These two tumors are disappeared. And there is a tumor on the liver of the same size. And after informed consent, we did the biopsy. So surprisingly, we detected the [INAUDIBLE] the CD8 positive T cells-- many, many CD8 positive T cells in the changed tumor. 04:22 So this is another patient, advanced hepatocellular carcinoma patient. So there is many hepatocellular carcinoma. And only after two peptide vaccinations, almost all tumors showed necrosis. But unfortunately, he died because of tumor thrombus at the right atrium. 04:50 This is data. Microscopically, these hepatocellular carcinoma tumor showed necrosis. And in pathologically, all the tumor showed central necrosis. And there is many CD8 positive T cells surrounding the tumor. 05:15 So in ovarian clear cell carcinoma, also showed glypican-3 expression. So in this patient, many kind of chemotherapy failed. And after that, peptide vaccination injected into the tumor. So two kinds of these tumor markers decreased after only peptide vaccination. In this patient there is a [INAUDIBLE] tumor metastasis of ovarian clear cell carcinoma. And they showed [INAUDIBLE] were enlarged and disappeared. This patients showed the partial response. 06:00 So in this advanced cancer only 3% to 5% patients showed clinical response, like partial response or complete response. So next study is adjuvant setting study after injection or larger [INAUDIBLE] treatment. So the treatment schedule is 10 times vaccination in a year after curative operation. 06:38 So we already published this data. So one year recurrence rate of 24% and control group is 50%. So glypican-3 peptide vaccine may prevent recurrence. 06:59 So this is a data, the overall survival data. So glypican-3 negative is a good prognosis factor. So glypican-3 negative patient showed good prognosis instead of peptide vaccination or surgery only. But glypican-3 positive patient showed bad prognosis without peptide vaccine. But peptide vaccine group showed good prognosis after vaccination. 07:34 So I already published the data phase I clinical trial of the pediatric cancer. So in this trial, five patients remission group of hepatoblastoma enrolled. So all hepatoblastoma patients showed without recurrence and good survival. 08:08 So this is a representative data of monitoring of peptide specific CTLs. This data is derived from interferon-gamma ex vivo [INAUDIBLE]. And this data is flow cytometry data using glypican-3 class I [INAUDIBLE]. So in this patient there is no peptide specific CTLs before pe」の翻訳
00:00 First colleague, Dr. Nakatsura from Tokyo. He's from National Cancer Center Hospital in Tokyo. He was unable to join us because of the typhoon. But he is safe and sound, and will be joining us via Zoom. And then we have Dr. Andrew Allen from Gritstone Oncology. So we're excited to hear a little bit more about from them about both peptide-based individual vaccines as well as personalized cancer vaccines. 00:30 So I think we're getting in touch with-- 00:32 Thank you. 00:32 There we go. Dr. Nakatsura? 00:35 Yeah, thank you. 00:36 Please take it away. 00:38 OK. Thank you, Johanna. 00:40 Thank you. 00:42 The title of today's talk is peptide-based individualized vaccines. At first I will show you the experiments using shared antigen glypican-3. And next I will show the plan of individualized vaccines. Glypican-3 is a carcinoembryonic antigen. And the shared antigen is the ideal target of anticancer immunotherapy against hepatocellular carcinoma. Glypican-3 is overexpressed in 80% of hepatocellular carcinoma. And in normal organs there is no expression. And there's expression at the placenta and fetal liver and fetal kidney at the messenger RNA level and protein level. 01:36 30% of hepatocellular carcinoma patient shows a glypican-3 negative. And they show the good prognosis. The glypican-3 is a bad prognosis of the 80% of hepatocellular carcinoma patient. 10 year survival rate is only 20%. 02:00 So this slide shows the outline of the mechanism of [INAUDIBLE] of peptide vaccine therapy. We injected the peptide with adjuvant injected intradermally or subcutaneously. The peptide is loaded on the dendritic cells at the skin. And at the lymph node, if there is a CTL have this receptor can recognize HLA class I and peptide complexes. And these CTL expand and increased and attack the cancer cells with this peptide on the HLA class I, but do not attack the normal cells. 02:56 So we completed the phase I clinical trial using glypican-3 peptide. So as you know, HLA-A2 is a common HLA in the Caucasian. 40% of Japanese has HLA-A2. And HLA-A24 is a measure in Japan. So 60% of Japanese have HLA-A24. We identified these kind of two peptides can induce peptide-specific CTLs. 03:29 And in present clinical trial, we experienced one partial response cases in the 33 patients. So in these patients, after only third vaccination there's tumor shrinkage. And this tumor shows necrosis. These two tumors are disappeared. And there is a tumor on the liver of the same size. And after informed consent, we did the biopsy. So surprisingly, we detected the [INAUDIBLE] the CD8 positive T cells-- many, many CD8 positive T cells in the changed tumor. 04:22 So this is another patient, advanced hepatocellular carcinoma patient. So there is many hepatocellular carcinoma. And only after two peptide vaccinations, almost all tumors showed necrosis. But unfortunately, he died because of tumor thrombus at the right atrium. 04:50 This is data. Microscopically, these hepatocellular carcinoma tumor showed necrosis. And in pathologically, all the tumor showed central necrosis. And there is many CD8 positive T cells surrounding the tumor. 05:15 So in ovarian clear cell carcinoma, also showed glypican-3 expression. So in this patient, many kind of chemotherapy failed. And after that, peptide vaccination injected into the tumor. So two kinds of these tumor markers decreased after only peptide vaccination. In this patient there is a [INAUDIBLE] tumor metastasis of ovarian clear cell carcinoma. And they showed [INAUDIBLE] were enlarged and disappeared. This patients showed the partial response. 06:00 So in this advanced cancer only 3% to 5% patients showed clinical response, like partial response or complete response. So next study is adjuvant setting study after injection or larger [INAUDIBLE] treatment. So the treatment schedule is 10 times vaccination in a year after curative operation. 06:38 So we already published this data. So one year recurrence rate of 24% and control group is 50%. So glypican-3 peptide vaccine may prevent recurrence. 06:59 So this is a data, the overall survival data. So glypican-3 negative is a good prognosis factor. So glypican-3 negative patient showed good prognosis instead of peptide vaccination or surgery only. But glypican-3 positive patient showed bad prognosis without peptide vaccine. But peptide vaccine group showed good prognosis after vaccination. 07:34 So I already published the data phase I clinical trial of the pediatric cancer. So in this trial, five patients remission group of hepatoblastoma enrolled. So all hepatoblastoma patients showed without recurrence and good survival. 08:08 So this is a representative data of monitoring of peptide specific CTLs. This data is derived from interferon-gamma ex vivo [INAUDIBLE]. And this data is flow cytometry data using glypican-3 class I [INAUDIBLE]. So in this patient there is no peptide specific CTLs before pe の定義
00:00 First colleague, Dr. Nakatsura from Tokyo. He's from National Cancer Center Hospital in Tokyo. He was unable to join us because of the typhoon. But he is safe and sound, and will be joining us via Zoom. And then we have Dr. Andrew Allen from Gritstone Oncology. So we're excited to hear a little bit more about from them about both peptide-based individual vaccines as well as personalized cancer vaccines. 00:30 So I think we're getting in touch with-- 00:32 Thank you. 00:32 There we go. Dr. Nakatsura? 00:35 Yeah, thank you. 00:36 Please take it away. 00:38 OK. Thank you, Johanna. 00:40 Thank you. 00:42 The title of today's talk is peptide-based individualized vaccines. At first I will show you the experiments using shared antigen glypican-3. And next I will show the plan of individualized vaccines. Glypican-3 is a carcinoembryonic antigen. And the shared antigen is the ideal target of anticancer immunotherapy against hepatocellular carcinoma. Glypican-3 is overexpressed in 80% of hepatocellular carcinoma. And in normal organs there is no expression. And there's expression at the placenta and fetal liver and fetal kidney at the messenger RNA level and protein level. 01:36 30% of hepatocellular carcinoma patient shows a glypican-3 negative. And they show the good prognosis. The glypican-3 is a bad prognosis of the 80% of hepatocellular carcinoma patient. 10 year survival rate is only 20%. 02:00 So this slide shows the outline of the mechanism of [INAUDIBLE] of peptide vaccine therapy. We injected the peptide with adjuvant injected intradermally or subcutaneously. The peptide is loaded on the dendritic cells at the skin. And at the lymph node, if there is a CTL have this receptor can recognize HLA class I and peptide complexes. And these CTL expand and increased and attack the cancer cells with this peptide on the HLA class I, but do not attack the normal cells. 02:56 So we completed the phase I clinical trial using glypican-3 peptide. So as you know, HLA-A2 is a common HLA in the Caucasian. 40% of Japanese has HLA-A2. And HLA-A24 is a measure in Japan. So 60% of Japanese have HLA-A24. We identified these kind of two peptides can induce peptide-specific CTLs. 03:29 And in present clinical trial, we experienced one partial response cases in the 33 patients. So in these patients, after only third vaccination there's tumor shrinkage. And this tumor shows necrosis. These two tumors are disappeared. And there is a tumor on the liver of the same size. And after informed consent, we did the biopsy. So surprisingly, we detected the [INAUDIBLE] the CD8 positive T cells-- many, many CD8 positive T cells in the changed tumor. 04:22 So this is another patient, advanced hepatocellular carcinoma patient. So there is many hepatocellular carcinoma. And only after two peptide vaccinations, almost all tumors showed necrosis. But unfortunately, he died because of tumor thrombus at the right atrium. 04:50 This is data. Microscopically, these hepatocellular carcinoma tumor showed necrosis. And in pathologically, all the tumor showed central necrosis. And there is many CD8 positive T cells surrounding the tumor. 05:15 So in ovarian clear cell carcinoma, also showed glypican-3 expression. So in this patient, many kind of chemotherapy failed. And after that, peptide vaccination injected into the tumor. So two kinds of these tumor markers decreased after only peptide vaccination. In this patient there is a [INAUDIBLE] tumor metastasis of ovarian clear cell carcinoma. And they showed [INAUDIBLE] were enlarged and disappeared. This patients showed the partial response. 06:00 So in this advanced cancer only 3% to 5% patients showed clinical response, like partial response or complete response. So next study is adjuvant setting study after injection or larger [INAUDIBLE] treatment. So the treatment schedule is 10 times vaccination in a year after curative operation. 06:38 So we already published this data. So one year recurrence rate of 24% and control group is 50%. So glypican-3 peptide vaccine may prevent recurrence. 06:59 So this is a data, the overall survival data. So glypican-3 negative is a good prognosis factor. So glypican-3 negative patient showed good prognosis instead of peptide vaccination or surgery only. But glypican-3 positive patient showed bad prognosis without peptide vaccine. But peptide vaccine group showed good prognosis after vaccination. 07:34 So I already published the data phase I clinical trial of the pediatric cancer. So in this trial, five patients remission group of hepatoblastoma enrolled. So all hepatoblastoma patients showed without recurrence and good survival. 08:08 So this is a representative data of monitoring of peptide specific CTLs. This data is derived from interferon-gamma ex vivo [INAUDIBLE]. And this data is flow cytometry data using glypican-3 class I [INAUDIBLE]. So in this patient there is no peptide specific CTLs before pe の例
00:00 First colleague, Dr. Nakatsura from Tokyo. He's from National Cancer Center Hospital in Tokyo. He was unable to join us because of the typhoon. But he is safe and sound, and will be joining us via Zoom. And then we have Dr. Andrew Allen from Gritstone Oncology. So we're excited to hear a little bit more about from them about both peptide-based individual vaccines as well as personalized cancer vaccines. 00:30 So I think we're getting in touch with-- 00:32 Thank you. 00:32 There we go. Dr. Nakatsura? 00:35 Yeah, thank you. 00:36 Please take it away. 00:38 OK. Thank you, Johanna. 00:40 Thank you. 00:42 The title of today's talk is peptide-based individualized vaccines. At first I will show you the experiments using shared antigen glypican-3. And next I will show the plan of individualized vaccines. Glypican-3 is a carcinoembryonic antigen. And the shared antigen is the ideal target of anticancer immunotherapy against hepatocellular carcinoma. Glypican-3 is overexpressed in 80% of hepatocellular carcinoma. And in normal organs there is no expression. And there's expression at the placenta and fetal liver and fetal kidney at the messenger RNA level and protein level. 01:36 30% of hepatocellular carcinoma patient shows a glypican-3 negative. And they show the good prognosis. The glypican-3 is a bad prognosis of the 80% of hepatocellular carcinoma patient. 10 year survival rate is only 20%. 02:00 So this slide shows the outline of the mechanism of [INAUDIBLE] of peptide vaccine therapy. We injected the peptide with adjuvant injected intradermally or subcutaneously. The peptide is loaded on the dendritic cells at the skin. And at the lymph node, if there is a CTL have this receptor can recognize HLA class I and peptide complexes. And these CTL expand and increased and attack the cancer cells with this peptide on the HLA class I, but do not attack the normal cells. 02:56 So we completed the phase I clinical trial using glypican-3 peptide. So as you know, HLA-A2 is a common HLA in the Caucasian. 40% of Japanese has HLA-A2. And HLA-A24 is a measure in Japan. So 60% of Japanese have HLA-A24. We identified these kind of two peptides can induce peptide-specific CTLs. 03:29 And in present clinical trial, we experienced one partial response cases in the 33 patients. So in these patients, after only third vaccination there's tumor shrinkage. And this tumor shows necrosis. These two tumors are disappeared. And there is a tumor on the liver of the same size. And after informed consent, we did the biopsy. So surprisingly, we detected the [INAUDIBLE] the CD8 positive T cells-- many, many CD8 positive T cells in the changed tumor. 04:22 So this is another patient, advanced hepatocellular carcinoma patient. So there is many hepatocellular carcinoma. And only after two peptide vaccinations, almost all tumors showed necrosis. But unfortunately, he died because of tumor thrombus at the right atrium. 04:50 This is data. Microscopically, these hepatocellular carcinoma tumor showed necrosis. And in pathologically, all the tumor showed central necrosis. And there is many CD8 positive T cells surrounding the tumor. 05:15 So in ovarian clear cell carcinoma, also showed glypican-3 expression. So in this patient, many kind of chemotherapy failed. And after that, peptide vaccination injected into the tumor. So two kinds of these tumor markers decreased after only peptide vaccination. In this patient there is a [INAUDIBLE] tumor metastasis of ovarian clear cell carcinoma. And they showed [INAUDIBLE] were enlarged and disappeared. This patients showed the partial response. 06:00 So in this advanced cancer only 3% to 5% patients showed clinical response, like partial response or complete response. So next study is adjuvant setting study after injection or larger [INAUDIBLE] treatment. So the treatment schedule is 10 times vaccination in a year after curative operation. 06:38 So we already published this data. So one year recurrence rate of 24% and control group is 50%. So glypican-3 peptide vaccine may prevent recurrence. 06:59 So this is a data, the overall survival data. So glypican-3 negative is a good prognosis factor. So glypican-3 negative patient showed good prognosis instead of peptide vaccination or surgery only. But glypican-3 positive patient showed bad prognosis without peptide vaccine. But peptide vaccine group showed good prognosis after vaccination. 07:34 So I already published the data phase I clinical trial of the pediatric cancer. So in this trial, five patients remission group of hepatoblastoma enrolled. So all hepatoblastoma patients showed without recurrence and good survival. 08:08 So this is a representative data of monitoring of peptide specific CTLs. This data is derived from interferon-gamma ex vivo [INAUDIBLE]. And this data is flow cytometry data using glypican-3 class I [INAUDIBLE]. So in this patient there is no peptide specific CTLs before pe の同義語
関連項目
