JP6991969B2 - 癌を治療するための方法及び組成物 - Google Patents
癌を治療するための方法及び組成物 Download PDFInfo
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Description
(a)白血球分離等の当分野で既知の方法によって、哺乳類供給源から得られる白血球画分を提供するステップと、
(b)向流遠心分離法によって、(a)のステップの白血球画分を4つ以上の細画分に分離するステップと、
(c)(b)のステップから得られた1以上の画分内の単球の、樹状細胞への転換を、前記細胞をカルシウムイオノホア、GM-CSF及びIL-13またはGM-CSF及びIL-4と接触させることで、刺激するステップと、
(d)(c)のステップから得られた、樹状細胞が濃縮された画分を特定するステップと、
(e)(d)のステップの濃縮画分を、好ましくは約4℃で収集するステップとを含む方法によって、DCが単離される。
・YMFPNAPYL(SEQ ID NO124;WT1-A1):CD8+応答を刺激する、変異アミノ酸R126Yを有するHLAクラスIペプチド。
・SGQAYMFPNAPYLPSCLES(SEQ ID NO125;WT1-122A1 long):前臨床及び第一相試験からのデータにしたがってCD4+及びCD8+応答の両方を刺激する、より長いペプチド内に埋め込まれたWT1-A1ヘテロクリティック配列を含むHLAクラスIIペプチド。
・RSDELVRHHNMHQRNMTKL(SEQ ID NO1; WT1-427 long)、及びPGCNKRYFKLSHLQMHSRKHTG(SEQ ID NO2;WT1-331 long):長期持続性CD8+T細胞応答の助けとなり得るCD4+応答を誘導するHLAクラスIIペプチド。
・患者を外来患者として扱う。
・WT1ワクチンを、0、2、4、6、8及び10週目に投与する。
・すべての注射を、四肢間を回転する部位に皮下投与する。
・すべての患者に、0日目及び2日目にサルグラモスチム(GM-CSF)70mcgを皮下注射する。患者は、SQ注射投与について適切に指示されている場合、GM-CSFを自己投与することができる。注射部位での刺激などの予期される反応を患者に知らせる。患者は注射の時間及び配置を記録した検査表を保管する。
・また、患者に、モンタニドと共にWT1ペプチドの1.0mlのエマルジョンを投与する。GM-CSFと同一の解剖学的部位で看護師が皮下投与する(自己投与でなくてよい)。
・ワクチン接種後約30分間患者を観察する。
・ニボルマブ、0、2、4、6、8、10、12週目に60分注入として静脈内投与する。対象には、前回のニボルマブ投与から少なくとも12日間以後に投与することができ、予定された投与日後3日以内に投与してもよい。3日間の期間後の投与は投与遅延とみなされる。処置は、前回の投与から最大6週間まで延期することができる。
[1]Siegel, R., D. Naishadham, and A. Jemal, Cancer statistics, 2012. CA Cancer J Clin, 2012. 62(1): p. 10-29
[2]Hoskins, W.J., C.A. Perez, and R.C. Young, Principles and practice of gynecologic oncology. 3rd ed. 2000, Philadelphia: Lippincott Williams & Wilkins. xxi, 1268 p.
[3]Barnhill, D.R., et al., The second-look surgical reassessment for epithelial ovarian carcinoma. Gynecol Oncol, 1984. 19(2): p. 148-54.
[4]Rubin, S.C., et al., Recurrence after negative second-look laparotomy for ovarian cancer: analysis of risk factors. Am J Obstet Gynecol, 1988. 159(5): p. 1094-8.
[5]Markman, M., et al., Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol, 1991. 9(3): p. 389-93.
[6]Zhang, H., et al., Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases. Cancer Res, 1998. 58(13): p. 2844-9.
[7]Zhang, L., et al., Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med, 2003. 348(3): p. 203-13.
[8]Curiel, T.J., et al., Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med, 2004. 10(9): p. 942-9.
[9]Iasonos, A., et al., Identifying clinical improvement in consolidation single-arm phase 2 trials in patients with ovarian cancer in second or greater clinical remission. Int J Gynecol Cancer, 2012. 22(1): p. 63-9.
[10]Berek, J.S., et al., Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. J Clin Oncol, 2004. 22(17): p. 3507-16.
[11]Reinartz, S., et al., Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II). Clin Cancer Res, 2004. 10(5): p. 1580-7.
[12]Bookman, M.A., et al., Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol, 2003. 21(2): p. 283-90.
[13]Allavena, P., et al., Intraperitoneal recombinant gamma-interferon in patients with recurrent ascitic ovarian carcinoma: modulation of cytotoxicity and cytokine production in tumor-associated effectors and of major histocompatibility antigen expression on tumor cells. Cancer Res, 1990. 50(22): p. 7318-23.
[14]Pujade-Lauraine, E., et al., Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy. J Clin Oncol, 1996. 14(2): p. 343-50.
[15]Recchia, F., et al., Interleukin-2 and 13-cis retinoic acid as maintenance therapy in advanced ovarian cancer. Int J Oncol, 2005. 27(4): p. 1039-46.
[16]Sabbatini, P.J., et al., Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial. Int J Cancer, 2000. 87(1): p. 79-85.
[17]Nicholson, S., et al., A phase I trial of idiotypic vaccination with HMFG1 in ovarian cancer. Cancer Immunol Immunother, 2004. 53(9): p. 809-16.
[18]Diefenbach, C.S., et al., Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission. Clin Cancer Res, 2008. 14(9): p. 2740-8.
[19]Keilholz, U., et al., Wilms' tumour gene 1 (WT1) in human neoplasia. Leukemia, 2005. 19(8): p. 1318-23.
[20]Oji, Y., et al., Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res, 1999. 90(2): p. 194-204.
[21]Scharnhorst, V., et al., Internal translation initiation generates novel WT1 protein isoforms with distinct biological properties. J Biol Chem, 1999. 274(33): p. 23456-62.
[22]Haber, D.A., et al., Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci U S A, 1991. 88(21): p. 9618-22.
[23]Mundlos, S., et al., Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in embryonic and adult tissues. Development, 1993. 119(4): p. 1329-41.
[24]Buckler, A.J., et al., Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development. Mol Cell Biol, 1991. 11(3): p. 1707-12.
[25]Fraizer, G.C., et al., Expression of the tumor suppressor gene WT1 in both human and mouse bone marrow. Blood, 1995. 86(12): p. 4704-6.
[26]Al-Hussaini, M., et al., WT1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma. Histopathology, 2004. 44(2): p. 109-15.
[27]Pinilla-Ibarz, J., et al., Improved human T-cell responses against synthetic HLA-0201 analog peptides derived from the WT1 oncoprotein. Leukemia, 2006. 20(11): p. 2025-33.
[28]May, R.J., et al., Peptide epitopes from the Wilms' tumor 1 oncoprotein stimulate CD4+ and CD8+ T cells that recognize and kill human malignant mesothelioma tumor cells. Clin Cancer Res, 2007. 13(15 Pt 1): p. 4547-55.
[29]Krug, L.M., et al., WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer. Cancer Immunol Immunother, 2010. 59(10): p. 1467-79.
[30]Oka, Y., et al., Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci U S A, 2004. 101(38): p. 13885-90.
[31]Letsch, A., et al., Effect of vaccination of leukemia patients with a MHC class I peptide of Wilms tumor gene 1 (WT1) peptide with unspecific T helper stimulation on WT1-specific IgM responses and on IgG responses. J Clin Oncol, 2008. 26: p. Abstr 3054.
[32]Ohno, S., et al., Wilms' tumor 1 (WT1) peptide immunotherapy for gynecological malignancy. Anticancer Res, 2009. 29(11): p. 4779-84.
[33]Schaed, S.G., et al., T-cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201+ melanoma patients: randomized trial comparing incomplete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, and QS-21 as immunological adjuvants. Clin Cancer Res, 2002. 8(5): p. 967-72.
[34]Slingluff, C.L., Jr., et al., Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol, 2003. 21(21): p. 4016-26.
[35]Faries, M.B., et al., Effect of granulocyte/macrophage colony-stimulating factor on vaccination with an allogeneic whole-cell melanoma vaccine. Clin Cancer Res, 2009. 15(22): p. 7029-35.
[36]Keilholz, U., et al., A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood, 2009. 113(26): p. 6541-8.
[37]Weber, J., et al., Granulocyte-macrophage-colony-stimulating factor added to a multipeptide vaccine for resected Stage II melanoma. Cancer, 2003. 97(1): p. 186-200.
[38]Keir, M.E., et al., PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol, 2008. 26: p. 677-704.
[39]Freeman, G.J., et al., Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med, 2000. 192(7): p. 1027-34.
[40]Latchman, Y., et al., PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol, 2001. 2(3): p. 261-8.
[41]Hamanishi, J., et al., Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A, 2007. 104(9): p. 3360-5.
[42]Mu, C.Y., et al., High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol, 2011. 28(3): p. 682-8.
[43]Pardoll, D.M., The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer, 2012. 12(4): p. 252-64.
[44]Nivolumab (BMS-936558) Investigator Brochure, Version 12. 2013.
[45]Hwang, W.T., et al., Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol, 2012. 124(2): p. 192-8.
[46]Matsuzaki, J., et al., Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A, 2010. 107(17): p. 7875-80.
[47]Brahmer, J.R., et al., Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 2012. 366(26): p. 2455-65.
[48]Page, D.B., et al., Immune modulation in cancer with antibodies. Annu Rev Med, 2014. 65: p. 185-202.
[49]Harrison, M.L., et al., Duration of second or greater complete clinical remission in ovarian cancer: exploring potential endpoints for clinical trials. Gynecol Oncol, 2007. 106(3): p. 469-75.
[50]Juretzka, M., et al., A phase 2 trial of oral imatinib in patients with epithelial ovarian, fallopian tube, or peritoneal carcinoma in second or greater remission. Eur J Gynaecol Oncol, 2008. 29(6): p. 568-72.
[51]Levine, D., et al., A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission. Cancer, 2007. 110(11): p. 2448-56.
[52]Walter, S., et al., Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med, 2012.
[53]Wolchok, J.D., et al., Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Ann N Y Acad Sci, 2013. 1291(1): p. 1-13.
[54]Hodi, F.S., et al., Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A, 2008. 105(8): p. 3005-10.
[55]Quezada, S.A., et al., CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest, 2006. 116(7): p. 1935-45.
[56]Duraiswamy, J., et al., Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res, 2013. 73(12): p. 3591-603.
[57]Wolchok, J.D., et al., Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res, 2009. 15(23): p. 7412-20.
[58]Dupont, J., et al., Wilms Tumor Gene (WT1) and p53 expression in endometrial carcinomas: a study of 130 cases using a tissue microarray. Gynecol Oncol, 2004. 94(2): p. 449-55.
[59]Eisenhauer, E.A., et al., New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 2009. 45(2): p. 228-47.
Claims (26)
- WT1発現癌を治療する、WT1発現癌の発生率を低減する、またはWT1発現癌に対する免疫応答を誘導するために使用される組成物であって、
(a)YMFPNAPYL(SEQ ID NO:124)、RSDELVRHHNMHQRNMTKL(SEQ ID NO:1)、PGCNKRYFKLSHLQMHSRKHTG(SEQ ID NO: 2)、及びSGQAYMFPNAPYLPSCLES(SEQ ID NO:125)を含むWT1ペプチドの組み合わせ、または、WT1ペプチドの前記組み合わせに特異的な細胞傷害性T細胞(CTL)を送達する1以上のWT1送達剤であって、
(i)WT1ペプチドの少なくとも1つの前記組み合わせ、
(ii)WT1ペプチドの少なくとも1つの前記組み合わせをコードする核酸、または
(iii)WT1ペプチドの少なくとも1つの前記組み合わせ、若しくは、WT1ペプチドの少なくとも1つの前記組み合わせをコードする核酸を含むか、若しくは、提示する免疫細胞、を含む、1以上のWT1送達剤と、
(b)前記WT1送達剤と組み合わせて使用される少なくとも1つの抗PD-1抗体と
を含む組成物。 - 前記CTLは、インビトロまたはエクスビボで作製されるか、またはドナーから取得されることを特徴とする請求項1に記載の組成物。
- 前記組成物は、担体、賦形剤、または希釈剤をさらに含むことを特徴とする請求項1に記載の組成物。
- 前記組成物は、アジュバントをさらに含むことを特徴とする請求項1に記載の組成物。
- 前記抗PD-1抗体は、ニボルマブ、ペンブロリズマブ、ピジリズマブ、若しくはMEDI-0680(AMP-514)、またはこれらの任意の組み合わせであることを特徴とする請求項1に記載の組成物。
- 前記1以上のWT1送達剤及び少なくとも1つの前記抗PD-1抗体は、同時に投与されるか、互いに重複した投与スケジュールで投与されるか、または前記WT1送達剤の投与後に前記抗PD-1抗体が投与されることを特徴とする請求項1記載の組成物。
- 前記WT1発現癌は、卵巣癌、中皮腫、白血病、ウィルムス腫瘍、急性骨髄性白血病(AML)、慢性骨髄性白血病(CML)、骨髄異形成症候群(MDS)、メラノーマ、胃癌、前立腺癌、胆道癌、泌尿器系癌、神経膠芽腫、軟部組織肉腫、骨肉腫、または非小細胞肺癌(NSCLC)であることを特徴とする請求項1記載の組成物。
- 前記アジュバントは、QS21、モンタニド、フロイント完全または不完全アジュバント、リン酸アルミニウム、水酸化アルミニウム、BCG、サイトカイン、またはミョウバンであることを特徴とする請求項4に記載の組成物。
- 前記各ペプチド200mcgをモンタニド ISA 51 VGによりエマルジョン化させ、0、2、4、6、8及び10週目に皮下投与することを特徴とする請求項1に記載の組成物。
- 前記抗PD-1抗体は、ニボルマブであることを特徴とする請求項5に記載の組成物。
- 3mg/kgのニボルマブを0、2、4、6、8、10及び12週目に静脈内投与することを特徴とする請求項10に記載の組成物。
- 前記WT1送達剤の単独投与、または抗PD-1抗体の単独投与の場合と比べて、WT1発現癌の治療、WT1発現癌の発生率の低減、またはWT1発現癌に対する免疫応答の誘導の効果が大きいことを特徴とする請求項1に記載の組成物。
- 前記CTLがインビトロまたはエクスビボで作製されるか、またはドナーから取得される場合、
前記抗PD-1抗体は、インビトロまたはエクスビボで含められるか、または前記ドナーに投与されることを特徴とする請求項2に記載の組成物。 - 対象に前記抗PD-1抗体がさらに投与されることを特徴とする請求項13に記載の組成物。
- 前記WT1送達剤は、前記(i)のWT1ペプチドの前記組み合わせを含むことを特徴とする請求項1に記載の組成物。
- は前記WT1送達剤、前記(ii)のWT1ペプチドの前記組み合わせをコードする前記核酸を含むことを特徴とする請求項1に記載の組成物。
- WT1ペプチドの前記組み合わせをコードする核酸は、ベクター内にあることを特徴とする請求項1に記載の組成物。
- 前記ベクターは、アデノウイルス、アデノ随伴ウイルス、レトロウイルス、レンチウイルス、ポックスウイルス、及びヘルペスウイルスからなる群より選択されるウイルスベクターであることを特徴とする請求項17に記載の組成物。
- 前記ベクターは、プラスミド、カチオン性脂質、リポソーム、及びウイルス様粒子からなる群より選択される非ウイルスベクターであることを特徴とする請求項17に記載の組成物。
- 前記ベクターは、自己細胞、同種細胞、細胞株、樹状細胞、抗原提示細胞、及びそれらの任意の組み合わせからなる群より選択される非ウイルスベクターであることを特徴とする請求項17に記載の組成物。
- 前記免疫細胞は、抗原提示細胞またはプロフェッショナル抗原提示細胞であることを特徴とする請求項1に記載の組成物。
- 前記抗原提示細胞または前記プロフェッショナル抗原提示細胞は、樹状細胞、マクロファージ、単球、またはB細胞であることを特徴とする請求項21に記載の組成物。
- WT1発現癌を治療する、WT1発現癌の発生率を低減する、またはWT1発現癌に対する免疫応答を誘導するために使用される組成物であって、
YMFPNAPYL(SEQ ID NO:124)、RSDELVRHHNMHQRNMTKL(SEQ ID NO:1)、PGCNKRYFKLSHLQMHSRKHTG(SEQ ID NO: 2)、及びSGQAYMFPNAPYLPSCLES(SEQ ID NO:125)を含むWT1ペプチドの組み合わせと、
WT1ペプチドの前記組み合わせと組み合わせて使用される、少なくとも1つの抗PD-1抗体と、を含むことを特徴とする組成物。 - 前記抗PD-1抗体は、ニボルマブ、ペンブロリズマブ、ピジリズマブ、MEDI-0680(AMP-514)またはこれらの任意の組み合わせであることを特徴とする請求項23に記載の組成物。
- 1以上の前記WT1送達剤及び少なくとも1つの前記抗PD-1抗体は、それぞれ個別に投与されることを特徴とする請求項1に記載の組成物。
- 前記癌は、卵巣癌、中皮腫、白血病、ウィルムス腫瘍、急性骨髄性白血病(AML)、慢性骨髄性白血病(CML)、骨髄異形成症候群(MDS)、メラノーマ、胃癌、前立腺癌、胆道癌、泌尿器系癌、神経膠芽腫、軟部組織肉腫、骨肉腫、または非小細胞肺癌(NSCLC)であることを特徴とする請求項23記載の組成物。
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WO2019006401A2 (en) * | 2017-06-30 | 2019-01-03 | Advaxis, Inc. | LISTERIA-BASED IMMUNOGENIC COMPOSITIONS COMPRISING HETERICCLIENT WILMS TUMOR PROTEIN ANTIGENS AND METHODS OF USE THEREOF |
EP3678701A4 (en) | 2017-09-05 | 2021-12-01 | Torque Therapeutics, Inc. | THERAPEUTIC PROTEIN COMPOSITIONS AND METHOD FOR MANUFACTURING AND USING THEREOF |
KR20200070405A (ko) * | 2017-11-08 | 2020-06-17 | 어드박시스, 인크. | 암 관련 단백질로부터의 면역원성 불규칙변화성 펩타이드 및 그것의 사용 방법 |
EP3737689A4 (en) | 2018-01-09 | 2021-12-01 | Cue Biopharma, Inc. | MULTIMERIC T CELL-MODULATING POLYPEPTIDES AND METHOD OF USING THEREOF |
US20210047363A1 (en) * | 2018-03-06 | 2021-02-18 | The United States Of America,As Represented By The Secretary,Department Of Health And Human Services | 17-beta-hydroxywithanolides and use thereof in treating cancer |
KR20210073540A (ko) * | 2018-10-05 | 2021-06-18 | 인터내셔널 인스티튜트 오브 캔서 이무놀로지 인코퍼레이티드 | 양성 종양의 예방 또는 치료약 |
TW202039542A (zh) * | 2018-12-19 | 2020-11-01 | 美商庫爾生物製藥有限公司 | 多聚體t細胞調節多肽及其使用方法 |
KR20220010712A (ko) * | 2019-04-10 | 2022-01-26 | 에스엘에스지 리미티드 엘엘씨 | Wt1-양성 암을 치료하기 위한 다가 면역요법 조성물 및 사용 방법 |
EP4085130A4 (en) | 2019-12-31 | 2024-04-10 | Elixirgen Therapeutics Inc | TEMPERATURE-BASED TRANSIENT DELIVERY OF NUCLEIC ACIDS AND PROTEINS TO CELLS AND TISSUES |
CN115666542A (zh) * | 2020-04-07 | 2023-01-31 | 梅塔诺伊治疗公司 | 用于治疗上皮性卵巢癌的乙醇胺调配物 |
MX2022013208A (es) | 2020-05-12 | 2022-11-14 | Cue Biopharma Inc | Polipeptidos multimericos moduladores de linfocitos t y metodos de uso de estos. |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014144885A2 (en) | 2013-03-15 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Cancer vaccines and methods of treatment using the same |
WO2015061752A1 (en) | 2013-10-25 | 2015-04-30 | Pharmacyclics, Inc. | Treatment using bruton's tyrosine kinase inhibitors and immunotherapy |
WO2015069770A1 (en) | 2013-11-05 | 2015-05-14 | Cognate Bioservices, Inc. | Combinations of checkpoint inhibitors and therapeutics to treat cancer |
WO2015103602A1 (en) | 2014-01-06 | 2015-07-09 | The Trustees Of The University Of Pennsylvania | Pd1 and pdl1 antibodies and vaccine combinations and use of same for immunotherapy |
WO2016186177A1 (ja) | 2015-05-20 | 2016-11-24 | 大日本住友製薬株式会社 | Wt1抗原ペプチドおよび免疫調節剤の併用 |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4722848A (en) | 1982-12-08 | 1988-02-02 | Health Research, Incorporated | Method for immunizing animals with synthetically modified vaccinia virus |
US5837249A (en) | 1985-04-19 | 1998-11-17 | The Wistar Institute | Method for generating an immunogenic T cell response protective against a virus |
AU1570292A (en) | 1991-02-07 | 1992-09-07 | Board Of Trustees Of The University Of Illinois, The | Conformationally restricted mimetics of beta turns and beta bulges and peptides containing the same |
WO1995004064A1 (en) | 1993-07-29 | 1995-02-09 | The Regents Of The University Of California | Polynucleotide decoys that ihnibit mhc-ii expression and uses thereof |
US5643786A (en) | 1995-01-27 | 1997-07-01 | The United States Of America As Represented By The Department Of Health And Human Services | Method for isolating dendritic cells |
AU4932199A (en) | 1998-07-31 | 2000-02-21 | Haruo Sugiyama | Cancer antigens based on tumor suppressor gene wt1 product |
US20030235557A1 (en) | 1998-09-30 | 2003-12-25 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
US7115272B1 (en) | 1998-09-30 | 2006-10-03 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
US7901693B2 (en) | 1998-09-30 | 2011-03-08 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
US7655249B2 (en) | 1998-09-30 | 2010-02-02 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
US7144581B2 (en) | 2000-10-09 | 2006-12-05 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
US7063854B1 (en) | 1998-09-30 | 2006-06-20 | Corixa Corporation | Composition and methods for WTI specific immunotherapy |
MXPA01003344A (es) * | 1998-09-30 | 2004-04-21 | Corixa Corp | Composiciones y metodos para inmunoterapia especifica de wt1. |
US7329410B1 (en) | 1998-09-30 | 2008-02-12 | Corixa Corporation | Compositions and method for WT1 specific immunotherapy |
WO2001025273A2 (en) | 1999-10-04 | 2001-04-12 | Corixa Corporation | Compositions and methods for wt1 specific immunotherapy |
US20030082194A1 (en) | 2000-02-22 | 2003-05-01 | Alexander Gaiger | Compositions and methods for diagnosis and therapy of malignant mesothelioma |
US7553494B2 (en) | 2001-08-24 | 2009-06-30 | Corixa Corporation | WT1 fusion proteins |
WO2003106682A1 (ja) | 2002-06-12 | 2003-12-24 | 中外製薬株式会社 | Hla−a24拘束性癌抗原ペプチド |
EP2343083B1 (en) | 2003-06-27 | 2014-01-15 | International Institute of Cancer Immunology, Inc. | Method of diagnosing cancer comprising the measurement of WT1-specific CTL precursor cells |
US20080070835A1 (en) | 2003-11-05 | 2008-03-20 | International Institute Of Cancer Immunology, Inc | Hla-Dr-Binding Antigen Peptide Derived From Wt1 |
US20060127409A1 (en) | 2003-12-01 | 2006-06-15 | Scheinberg David A | Bcr-abl vaccines and methods of use thereof |
EP1708732B2 (en) | 2003-12-01 | 2016-05-18 | Sloan-Kettering Institute For Cancer Research | Synthetic hla binding peptide analogues and uses thereof |
US8765687B2 (en) | 2005-10-17 | 2014-07-01 | Sloan Kettering Institute For Cancer Research | WT1 HLA class II-binding peptides and compositions and methods comprising same |
DE102006014261A1 (de) | 2006-03-28 | 2007-10-04 | Dr.Ing.H.C. F. Porsche Ag | Luftleitvorrichtung für ein Fahrzeug |
CA2645766A1 (en) | 2006-04-10 | 2007-10-25 | Sloan Kettering Institute For Cancer Research | Immunogenic wt-1 peptides and methods of use thereof |
CA2881594C (en) | 2007-12-05 | 2016-04-12 | International Institute Of Cancer Immunology, Inc. | Cancer vaccine composition |
US20110136141A1 (en) | 2009-12-03 | 2011-06-09 | Abbott Laboratories | Peptide reagents and method for inhibiting autoantibody antigen binding |
EP3520810A3 (en) | 2012-01-13 | 2019-11-06 | Memorial Sloan-Kettering Cancer Center | Immunogenic wt1 peptides and use thereof |
US9919037B2 (en) | 2013-01-15 | 2018-03-20 | Memorial Sloan Kettering Cancer Center | Immunogenic WT-1 peptides and methods of use thereof |
CN103961702B (zh) * | 2013-02-05 | 2019-04-09 | 日东电工株式会社 | 粘膜给予用wt1肽癌症疫苗组合物 |
US9364523B2 (en) | 2014-03-17 | 2016-06-14 | Tapimmune Inc. | Chimeric nucleic acid molecule with non-AUG translation initiation sequences |
CN116327903A (zh) | 2015-11-20 | 2023-06-27 | 纪念斯隆凯特林癌症中心 | 用于治疗癌症的方法和组合物 |
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- 2023-12-27 JP JP2023220529A patent/JP2024041809A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014144885A2 (en) | 2013-03-15 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Cancer vaccines and methods of treatment using the same |
WO2015061752A1 (en) | 2013-10-25 | 2015-04-30 | Pharmacyclics, Inc. | Treatment using bruton's tyrosine kinase inhibitors and immunotherapy |
WO2015069770A1 (en) | 2013-11-05 | 2015-05-14 | Cognate Bioservices, Inc. | Combinations of checkpoint inhibitors and therapeutics to treat cancer |
WO2015103602A1 (en) | 2014-01-06 | 2015-07-09 | The Trustees Of The University Of Pennsylvania | Pd1 and pdl1 antibodies and vaccine combinations and use of same for immunotherapy |
WO2016186177A1 (ja) | 2015-05-20 | 2016-11-24 | 大日本住友製薬株式会社 | Wt1抗原ペプチドおよび免疫調節剤の併用 |
Non-Patent Citations (4)
Title |
---|
KRUG, L.M. et al.,Cancer Immunol Immunother,2010年,Vol. 59,pp. 1467-79/二次文献 pp. 1-25 |
LIM, K.P. et al.,J Immunother,2011年,Vol. 34, No. 9,pp. 704 |
MASLAK, P.G. et al.,Blood,2010年,Vol. 116,pp. 171-9 |
RIETHER, C. et al.,Leukemia,2015年02月,Vol. 29,pp. 1781-5 |
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MD3377516T2 (ro) | 2022-10-31 |
CA3005896A1 (en) | 2017-05-26 |
US20180339030A1 (en) | 2018-11-29 |
JP2024041809A (ja) | 2024-03-27 |
CN116327902A (zh) | 2023-06-27 |
WO2017087857A1 (en) | 2017-05-26 |
CN108431022A (zh) | 2018-08-21 |
DK3377516T3 (da) | 2022-09-19 |
LT3377516T (lt) | 2022-09-26 |
EP3377516B1 (en) | 2022-06-15 |
SI3377516T1 (sl) | 2023-01-31 |
RS63561B1 (sr) | 2022-10-31 |
ES2926386T3 (es) | 2022-10-25 |
JP2022033926A (ja) | 2022-03-02 |
HRP20220994T1 (hr) | 2022-11-11 |
CN115920017A (zh) | 2023-04-07 |
HUE059694T2 (hu) | 2022-12-28 |
PT3377516T (pt) | 2022-09-23 |
MA43283B1 (fr) | 2022-08-31 |
EP3377516A4 (en) | 2019-06-26 |
EP3377516A1 (en) | 2018-09-26 |
JP2018538265A (ja) | 2018-12-27 |
PL3377516T3 (pl) | 2022-10-10 |
MA43283A (fr) | 2018-09-26 |
EP4130026A1 (en) | 2023-02-08 |
AU2016356708B2 (en) | 2022-02-03 |
CN116327903A (zh) | 2023-06-27 |
AU2022202973A1 (en) | 2022-05-26 |
KR20180094922A (ko) | 2018-08-24 |
US11033613B2 (en) | 2021-06-15 |
CN108431022B (zh) | 2022-08-09 |
AU2016356708A1 (en) | 2018-07-05 |
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