JP2012180359A - メラノーマ関連mhcクラスi関連オリゴペプチドおよびその使用 - Google Patents
メラノーマ関連mhcクラスi関連オリゴペプチドおよびその使用 Download PDFInfo
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- JP2012180359A JP2012180359A JP2012097324A JP2012097324A JP2012180359A JP 2012180359 A JP2012180359 A JP 2012180359A JP 2012097324 A JP2012097324 A JP 2012097324A JP 2012097324 A JP2012097324 A JP 2012097324A JP 2012180359 A JP2012180359 A JP 2012180359A
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Classifications
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- A—HUMAN NECESSITIES
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00119—Melanoma antigens
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Abstract
【解決手段】CD8陽性細胞傷害性Tリンパ球(CTL)によってペプチド抗原として認識され、CTLに誘導される腫瘍細胞の溶解および/またはアポトーシスを誘発する特定のメラノーマ関連オリゴペプチドに関する。
【選択図】なし
Description
腫瘍ワクチンを開発する主な目的は、CD8+CTLに認識される腫瘍関連抗原の同定および性質決定である。
‐腫瘍での遺伝的および後成的事象に起因する、悪性腫瘍の(同様の組織学的起源でさえ)個体間で多様な抗原表現型、
‐HLA対立遺伝子の明白な多型、
‐特定のエピトープに反応する個々のT細胞レパートリーの能力にある。
チロシナーゼ/HLA‐Cw5;MAGE‐A3/HLA‐Cw2;MAGE‐A6/HLA‐Cw2;MAGE‐A4/HLA‐B27およびMAGE‐A4/HLA‐Cw5
メラン‐A/HLA−B51;gp100/HLA‐A24;MAGE‐A3/HLA‐A24;MAGE‐A6/HLA‐A24;MAGE‐C2/HLA‐A24;MAGE‐C2/HLA−B7;MAGE‐C2/HLA‐Cw7およびMAGE‐C2/HLA‐Cw15
T. Wolfel, A. Van Pel, E. De Plaen, C. Lurquin, J. Maryanski and T. Boon. Immunogenic (tum-) variants obtained by mutagenesis of mouse mastocytoma P815. VIII. Detection of stable transfectants expressing a tum- antigen with a cytolytic T cell stimulation assay. Immunogenetics 26: 178-187, 1987.
T. Wolfel, E. Klehmann, C. Muller, K.-H. Schutt, K.-H. Meyer zum Buschenfelde and A. Knuth. Lysis of human melanoma cells by autologous cytolytic T cell (CTL) clones: Identification of HLA-A2 as a restriction element for three different antigens. J. Exp. Med. 170 :797-810, 1989.
V. Brichard, A. Van Pel, T. Wolfel, C. Wolfel, E. de Plaen, B. Leth?, P. Coulie, and T. Boon. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J. Exp. Med. 178: 489-495, 1993.
T. Wolfel, A. Van Pel, V. Brichard, J. Schneider, B. Seliger, K.-H. Meyer zum Buschenfelde, and T. Boon. Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur. J. Immunol. 24:759-764, 1994.
P. Coulie, V. Brichard, A. Van Pel, T. Wolfel, J. Schneider, C. Traversari, S. Mattei, E. De Plaen, C. Lurquin, J.-P. Szikora, J.-C. Renauld, and T. Boon. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J. Exp. Med. 180:35-42, 1994.
T. Wolfel, M. Hauer, J. Schneider, M. Serrano, C. Wolfel, E. Klehmann-Hieb, E. De Plaen, T.Hankeln, K.-H. Meyer zum Buschenfelde, and D. Beach. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281-1284, 1995.
V. G. Brichard, J. Herman, A. Van Pel, C. Wildman, B. Gaugler, T. Wolfel, T. Boon, and B. Leth?. A tyrosinase peptide presented by HLA-B44 is recognized by autologous cytolytic T lymphocytes. Eur. J. Immunol. 26:224-230, 1996.
W. Herr, J. Schneider, A.W. Lohse, K.-H. Meyer zum Buschenfelde, and T. Wolfel. Detection and quantification of blood-derived T lymphocytes secreting tumor necrosis factor alpha in response to HLA-A2.1-binding melanoma and viral peptide antigens. J.Immunol. Methods 191:131-142, 1996.
W. Herr, B. Linn, N. Leister, E. Wandel, K.-H. Meyer zum Buschenfelde, and T. Wolfel. The use of computer-assisted video image analysis for the quantification of CD8+ T lymphocytes producing tumor necrosis factor a spots in response to peptide antigens. J. Immunol. Methods 203:141-152, 1997.
J. Schneider, V. Brichard, T. Boon, K.-H. Meyer zum Buschenfelde, and T. Wolfel. Overlapping peptides of melanocyte differentiation antigen Melan-A/MART-1 recognized byautologous cytolytic T lymphocytes in association with HLA-B45.1 and HLA-A2.1. Int. J. Cancer 75:451-458, 1998.
S. Morel, A. Ooms, A. Van Pel, T. Wolfel, V. Brichard, P. van der Bruggen, B. Van den Eynde and G. Degiovanni. A new tyrosinase peptide presented by HLA-B35 is recognized on a human melanoma by autologous cytotoxic T lymphocytes. Int. J. Cancer 83:755-759, 1999.
C.Wolfel, I.Drexler, A. Van Pel, T. Thres, N. Leister, W. Herr, G. Sutter, C. Huber and T. Wolfel. Transporter (TAP)- and proteasome-independent presentation of a melanoma-associated tyrosinase epitope. Int. J. Cancer 88:432-438, 2000.
C.M.Britten, R.G.Meyer, T.Kreer, I.Drexler, T.Wolfel, W.Herr. The use of HLA-A*0201-transfected K562 as standard antigen-presenting cells for CD8(+) T lymphocytes in IFN-gamma ELISPOT assays. J. Immunol. Methods 259:95-110, 2002.
R.Konopitzky, U.Konig, R.G.Meyer, W.Sommergruber, T.Wolfel, and T.Schweighoffer. Identification of HLA-A*0201-restricted T cell epitopes derived from the novel overexpressed tumor antigen CLCA2. J. Immunol., 169:540-547, 2002.
C.M.Britten, R.G.Meyer, N.Frankenberg, C.Huber. T.Wolfel. The use of clonal mRNA as antigenic format for the detection of antigen-specific T lymphocytes in IFN-gamma ELISPOT assays. J. Immunol. Methods, 287:125-136, 2004.
A.Dorrschuck, A.Schmidt, E. Schnurer, M. Gluckmann, C.Albrecht, C.Wolfel, V.Lennerz, A.Lifke, C.Di Natale, E.Ranieri, L.Gesualdo, C.Huber, M.Karas, T.Wolfel, and W.Herr. CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA-class Ia/Ib-associated renal carcinoma antigens with ubiquitous or restricted tissue expression. Blood, 104:2591-2599, 2004.
Y.Zhang. Z.Sun. H.Nicolay, R.G.Meyer, N.Renkvist, V.Stroobant, J.Corthals, J.Carrasco, A.M.Eggermont, M.Marchand, K.Thielemans, T.Wolfel, T.Boon, P.van der Bruggen. Monitoring of anti-vaccine CD4 T cell frequencies in melanoma patients vaccianted with a MAGE-3 protein. J. Immunol. 174:2404-2411, 2005.
R.G.Meyer, C.M.Britten, U.Siepmann, B.Petzold, T.A.Sagban, H.A.Lehr, B. Weigle, M.Schmitz, L.Mateo, B.Schmidt, H.Bernhard, T.Jakob, R.Hein, G.Schuler, B.Schuler-Thurner, S.N. Wagner, I.Drexler, G.Sutter, N.Arndtz, P.Chaplin, A.Enk, C.Huber, and T.Wolfel. A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia virus Ankara (MVA-hTyr). Cancer Immunol. Immunother. 54:453-467, 2005.
C.M.Britten, R.G.Meyer, C.Graf, C.Huber, T.Wolfel. Identification of T cell epitopes by the use of rapidly generated mRNA fragments. J. Immunol. Methods 299:165-175, 2005.
Claims (22)
- 免疫原は9〜約15残基長のペプチドであり、配列番号2、3、6、7、8、9、10、11、12、1、4および5から選択されるアミノ酸配列を含み、該免疫原はメラノーマに特異的なHLAによって制限されるCTL応答を誘発し、該ペプチドは基礎となる腫瘍抗原の全長配列には対応していない、メラノーマに特異的な免疫原。
- 該免疫原が9〜11残基長である請求項1記載の免疫原。
- 該免疫原が配列番号2、3、6、7、8、9、10、11、12、1、4および5のペプチドの1つと同一である請求項1記載の免疫原。
- 該免疫原のアミノ酸配列はアミノ酸の置換、欠失、挿入、付加、逆位によって、および/または該配列の1つ以上のアミノ酸の化学的または物理的修飾によって誘導化が可能であり、該アミノ酸配列は配列番号1〜12のペプチドの1つのアミノ酸配列に機能的に同等であり、該免疫原はCD8陽性CTLに対するエピトープであり、腫瘍細胞に対するCD8陽性CTLの免疫応答を誘発可能であり、該免疫応答はMHCクラスI、対立遺伝子変異体AまたはBの分子群のヒト白血球抗原に制限されている請求項1〜3のいずれかに記載の免疫原。
- ‐NH‐CO‐結合または‐CO‐NH‐ペプチド結合の代わりに他の非ペプチド結合で設計され、請求項1〜4のいずれかに記載の免疫原に対応することを特徴とする、レトロ逆位ペプチドまたは擬ペプチド。
- 請求項1〜5のいずれかに記載の免疫原またはレトロ逆位ペプチドまたは擬ペプチド、HLA分子の重鎖および自由リンカーからなり、該免疫原またはレトロ逆位ペプチドまたは擬ペプチドがHLA分子のペプチド結合溝を占有するように設計された融合タンパク質。
- 請求項1〜4のいずれかに記載の免疫原または請求項6記載の融合タンパク質をコードするヌクレオチド配列を含むポリヌクレオチド。
- 請求項1〜4のいずれかに記載の少なくとも1つの免疫原および/または請求項5記載の少なくとも1つのレトロ逆位ペプチドもしくは擬ペプチドおよび/または請求項6記載の融合タンパク質および/または請求項7記載のポリヌクレオチドを含み、任意にそれぞれ許容可能な担体および賦形剤と共に含む組成物であることを特徴とする、T細胞、特にCD8陽性細胞傷害性Tリンパ球をインビボまたはインビトロで活性化する医薬組成物。
- 請求項7記載の少なくとも1つ以上のポリヌクレオチドを含み、自己、同種、異種または微生物起源の細胞において発現可能な組換えDNAまたはRNAベクター分子。
- 請求項7記載のポリヌクレオチドまたは請求項9のベクター分子を含む宿主細胞。
- 各免疫原に対する、あるいは各免疫原とHLAとの複合体に対するポリクローナル、モノクローナルまたは組換え抗体を産生するための、請求項1〜4のいずれかに記載の少なくとも1つの免疫原および/または請求項5記載のレトロ逆位ペプチドもしくは擬ペプチドおよび/または請求項7記載の融合タンパク質の使用。
- 請求項1〜4のいずれかに記載の少なくとも1つの免疫原および/または請求項5記載のレトロ逆位ペプチドもしくは擬ペプチドおよび/または請求項7記載の融合タンパク質と、あるいは各免疫原とHLAとの複合体と特異的に反応する抗体。
- 各免疫原に対するポリクローナルまたはモノクローナルまたは組換えT細胞受容体またはそれらと機能的に同等の分子を生産するための、請求項1〜4のいずれかに記載の少なくとも1つの免疫原および/または請求項5記載のレトロ逆位ペプチドもしくは擬ペプチドおよび/または請求項7記載の融合タンパク質の使用。
- 請求項1〜4のいずれかに記載の少なくとも1つの免疫原および/または請求項5記載のレトロ逆位ペプチドもしくは擬ペプチドおよび/または請求項7記載の融合タンパク質と特異的に反応するT細胞受容体またはそれと機能的に同等の分子。
- 請求項14記載のT細胞受容体をコードするポリヌクレオチド。
- 請求項14記載のT細胞受容体を発現する発現ベクター。
- 請求項15記載のポリヌクレオチドまたは請求項16記載の発現ベクターを含む宿主細胞。
- 少なくとも1つの免疫原および/または少なくとも1つのレトロ逆位ペプチドもしくは擬ペプチドおよび/または少なくとも1つの融合タンパク質および/または少なくとも1つのポリヌクレオチドおよび/または少なくとも1つのT細胞受容体および/または少なくとも1つのベクター分子および/または少なくとも1つの宿主細胞および/または前記請求項のいずれかに記載の少なくとも1つの抗体を含み、任意に好適な添加剤および賦形剤と共に含む医薬組成物であることを特徴とする、請求項1〜4のいずれかに記載の免疫原の1つに関連する疾患治療用医薬組成物。
- T細胞、特にCD8陽性細胞傷害性Tリンパ球の活性化および機能状態を検出および/または影響および/または生成および/または増加および/または制御するための診断剤および/または治療剤および/または予防剤を生産するための、請求項1〜4のいずれかに記載の免疫原および/または請求項5記載のレトロ逆位ペプチドもしくは擬ペプチドおよび/または請求項7記載の融合タンパク質の使用。
- 腫瘍治療または腫瘍形成予防処置に関連する免疫反応を誘発するための請求項1〜4のいずれかに記載の免疫原および/または請求項5記載のレトロ逆位ペプチドもしくは擬ペプチドおよび/または請求項7記載の融合タンパク質の使用。
- 前記請求項のいずれかに記載の少なくとも1つの免疫原および/または少なくとも1つのレトロ逆位ペプチドもしくは擬ペプチドおよび/または少なくとも1つの融合タンパク質および/または少なくとも1つのポリヌクレオチドおよび/または少なくとも1つのT細胞受容体および/または少なくとも1つのベクター分子および/または少なくとも1つの宿主細胞および/または少なくとも1つの抗体の治療有効量を投与し、それにより治療効果を達成することを含む、メラノーマ患者の治療方法。
- 請求項1〜4のいずれかに記載のメラノーマに特異的な免疫原の応答誘発量を投与することを含む、メラノーマに特異的なCTL応答を誘発する方法。
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DE102005046490A1 (de) | 2005-09-28 | 2007-03-29 | Johannes-Gutenberg-Universität Mainz | Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen |
DE102006060824B4 (de) | 2006-12-21 | 2011-06-01 | Johannes-Gutenberg-Universität Mainz | Nachweis von individuellen T-Zell-Reaktionsmustern gegen Tumor-assoziierte Antigene (TAA) in Tumorpatienten als Basis für die individuelle therapeutische Vakzinierung von Patienten |
CN102164941B (zh) | 2008-04-18 | 2015-05-27 | 里亚塔医药公司 | 抗氧化剂炎症调节剂:具有饱和c环的齐墩果酸衍生物 |
JP5564490B2 (ja) | 2008-04-18 | 2014-07-30 | リアタ ファーマシューティカルズ インコーポレイテッド | 抗炎症性ファルマコアを含む化合物および使用法 |
WO2010093993A2 (en) | 2009-02-12 | 2010-08-19 | Human Genome Sciences, Inc. | Use of b lymphocyte stimulator protein antagonists to promote transplantation tolerance |
AU2012261237B2 (en) | 2011-05-24 | 2017-06-01 | BioNTech SE | Individualized vaccines for cancer |
WO2013143555A1 (en) | 2012-03-26 | 2013-10-03 | Biontech Ag | Rna formulation for immunotherapy |
EP2925348B1 (en) | 2012-11-28 | 2019-03-06 | BioNTech RNA Pharmaceuticals GmbH | Individualized vaccines for cancer |
WO2014180490A1 (en) | 2013-05-10 | 2014-11-13 | Biontech Ag | Predicting immunogenicity of t cell epitopes |
CA2960834A1 (en) | 2014-09-10 | 2016-03-17 | Genentech, Inc. | Immunogenic mutant peptide screening platform |
WO2016045732A1 (en) | 2014-09-25 | 2016-03-31 | Biontech Rna Pharmaceuticals Gmbh | Stable formulations of lipids and liposomes |
WO2016128060A1 (en) | 2015-02-12 | 2016-08-18 | Biontech Ag | Predicting t cell epitopes useful for vaccination |
GB201507719D0 (en) * | 2015-05-06 | 2015-06-17 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides and scaffolds thereof for use in immunotherapy against colorectal carcinoma (CRC) and other cancers |
WO2017059902A1 (en) | 2015-10-07 | 2017-04-13 | Biontech Rna Pharmaceuticals Gmbh | 3' utr sequences for stabilization of rna |
EP3419656A4 (en) * | 2016-02-22 | 2019-10-30 | Oceanside Biotechnology | NEOANTIGEN COMPOSITIONS AND THEIR METHODS OF USE IN IMMUNO-ONCOTHERAPY |
TW201906859A (zh) | 2017-07-07 | 2019-02-16 | 德商英麥提克生物技術股份有限公司 | 用於肺癌(包括 nsclc、sclc 和其他癌症)免疫治療的新型肽和肽組合物 |
WO2019007974A1 (en) | 2017-07-07 | 2019-01-10 | Immatics Biotechnologies Gmbh | NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY OF LUNG CANCER, INCLUDING NSCLC, CPPC AND OTHER CANCERS |
DE102018107224A1 (de) | 2018-02-21 | 2019-08-22 | Immatics Biotechnologies Gmbh | Peptide und Kombinationen von Peptiden nicht-kanonischen Ursprungs zur Verwendung in der Immuntherapie gegen verschiedene Krebsarten |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4003A (en) * | 1845-04-16 | Cochrane | ||
US5025A (en) * | 1847-03-20 | Horatio allen | ||
WO2000024778A1 (en) * | 1998-10-26 | 2000-05-04 | The Government Of The United States Of America Represented By The Secretary, Department Of Health And Human Services | Hla-a2 and hla-dr specific peptide epitopes from the melanoma antigen trp2 |
JP2003501025A (ja) * | 1999-05-27 | 2003-01-14 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 腫瘍関連抗原(c42) |
JP2004500024A (ja) * | 1999-04-28 | 2004-01-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 腫瘍関連抗原 |
WO2004029071A2 (en) * | 2002-09-27 | 2004-04-08 | Ludwig Institute For Cancer Research | Mage-c2 antigenic peptides and uses thereof |
JP2009511424A (ja) * | 2005-09-01 | 2009-03-19 | ヨハネス グーテンベルク ウニベルジテート マインツ | メラノーマ関連mhcクラスi関連オリゴペプチドおよびその使用 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0921805A4 (en) * | 1996-03-19 | 2002-06-26 | Univ Virginia | PEPTIDES DETECTED BY MELANOMA-SPECIFIC A1, A2 AND A3 RESTRICTED CYTOTOXIC LYMPHOCYTES, AND THEIR USE |
US6027924A (en) * | 1997-04-25 | 2000-02-22 | Ludwig Institute For Cancer Research | Isolated nucleic acid molecule coding for tumor rejection antigen precursor MAGE-C1 and uses thereof |
GB9908263D0 (en) * | 1999-04-13 | 1999-06-02 | Binding Site The Limited | Eliciting improved immune responses |
DE19936563A1 (de) * | 1999-08-04 | 2001-02-08 | Boehringer Ingelheim Int | Tumorassoziiertes Antigen |
AU1013601A (en) * | 1999-10-22 | 2001-05-08 | Aventis Pasteur Limited | Method of inducing and/or enhancing an immune response to tumor antigens |
AUPQ776100A0 (en) * | 2000-05-26 | 2000-06-15 | Australian National University, The | Synthetic molecules and uses therefor |
WO2002036142A2 (en) * | 2000-11-03 | 2002-05-10 | University Of Vermont And State Agricultural College | Compositions for inhibiting grb7 |
US20040053822A1 (en) * | 2000-12-11 | 2004-03-18 | John Fikes | Inducing cellular immune responses to mage2/3 using peptide and nucleic acid compositions |
FR2830940B1 (fr) * | 2001-10-17 | 2007-06-15 | Commissariat Energie Atomique | Procede de selection de ligands d'hla-dp4 et ses applications |
WO2003100027A2 (en) * | 2002-05-28 | 2003-12-04 | Baylor College Of Medicine | Mutant fibronectin and tumor metastasis |
US7311914B2 (en) * | 2002-08-13 | 2007-12-25 | Ludwig Institute For Cancer Research | MAGE-A4 antigenic peptides and uses thereof |
EP1578432A4 (en) * | 2002-10-03 | 2008-07-30 | Epimmune Inc | HLA BINDING PEPTIDES AND USES THEREOF |
US7807392B1 (en) * | 2003-09-15 | 2010-10-05 | Celera Corporation | Lung disease targets and uses thereof |
IL158140A0 (en) * | 2003-09-25 | 2004-03-28 | Hadasit Med Res Service | Multiepitope polypeptides for cancer immunotherapy |
-
2005
- 2005-09-01 DE DE102005041616A patent/DE102005041616B4/de not_active Expired - Fee Related
-
2006
- 2006-08-31 WO PCT/EP2006/008533 patent/WO2007025760A2/de active Application Filing
- 2006-08-31 US US11/991,339 patent/US20090104186A1/en not_active Abandoned
- 2006-08-31 JP JP2008528423A patent/JP5363105B2/ja not_active Expired - Fee Related
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-
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- 2012-04-23 JP JP2012097324A patent/JP5663522B2/ja not_active Expired - Fee Related
-
2015
- 2015-07-07 US US14/792,919 patent/US20150366957A1/en not_active Abandoned
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4003A (en) * | 1845-04-16 | Cochrane | ||
US5025A (en) * | 1847-03-20 | Horatio allen | ||
WO2000024778A1 (en) * | 1998-10-26 | 2000-05-04 | The Government Of The United States Of America Represented By The Secretary, Department Of Health And Human Services | Hla-a2 and hla-dr specific peptide epitopes from the melanoma antigen trp2 |
JP2004500024A (ja) * | 1999-04-28 | 2004-01-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 腫瘍関連抗原 |
JP2003501025A (ja) * | 1999-05-27 | 2003-01-14 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 腫瘍関連抗原(c42) |
WO2004029071A2 (en) * | 2002-09-27 | 2004-04-08 | Ludwig Institute For Cancer Research | Mage-c2 antigenic peptides and uses thereof |
JP2009511424A (ja) * | 2005-09-01 | 2009-03-19 | ヨハネス グーテンベルク ウニベルジテート マインツ | メラノーマ関連mhcクラスi関連オリゴペプチドおよびその使用 |
Non-Patent Citations (6)
Title |
---|
JPN6010037612; Bonehill A: 'Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and cl' J Immunol. Vol.172 no.11, 20040601, pp.6649-6657 * |
JPN6012002102; Russo V et al.: 'Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-res' Proc Natl Acad Sci U S A. Vol.97 no.5, 20000229, pp.2185-2190 * |
JPN6012002104; Reynolds SR: 'Identification of HLA-A*03, A*11 and B*07-restricted melanoma-associated peptides that are immunogen' J Immunol Methods. Vol.244 no.1-2, 20001020, pp.59-67 * |
JPN6012002108; Meziere C et al.: 'In vivo T helper cell response to retro-inverso peptidomimetics.' J Immunol. Vol.159 no.7, 19971001, pp.3230-3237 * |
JPN6012044120; Notter M and Schirrmacher V: 'Tumor-specific T-cell clones recognize different protein determinants of autologous human malignant' Int J Cancer. Vol.45 No.5, 19900515, pp.834-841 * |
JPN6013064041; Ma W et al.: 'Two new tumor-specific antigenic peptides encoded by gene MAGE-C2 and presented to cytolytic T lymph' Int J Cancer. Vol.109 No.5, 20040501, pp.698-702 * |
Also Published As
Publication number | Publication date |
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EP1919943A2 (de) | 2008-05-14 |
US20150366957A1 (en) | 2015-12-24 |
ATE461939T1 (de) | 2010-04-15 |
EP1919943B1 (de) | 2010-03-24 |
DE502006006521D1 (de) | 2010-05-06 |
US20090104186A1 (en) | 2009-04-23 |
DE102005041616A8 (de) | 2008-05-29 |
DE102005041616B4 (de) | 2011-03-17 |
JP5363105B2 (ja) | 2013-12-11 |
WO2007025760A3 (de) | 2007-06-07 |
JP5663522B2 (ja) | 2015-02-04 |
JP2009511424A (ja) | 2009-03-19 |
WO2007025760A2 (de) | 2007-03-08 |
DE102005041616A1 (de) | 2007-03-08 |
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