JP2016510030A5 - - Google Patents
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- JP2016510030A5 JP2016510030A5 JP2015560330A JP2015560330A JP2016510030A5 JP 2016510030 A5 JP2016510030 A5 JP 2016510030A5 JP 2015560330 A JP2015560330 A JP 2015560330A JP 2015560330 A JP2015560330 A JP 2015560330A JP 2016510030 A5 JP2016510030 A5 JP 2016510030A5
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| CN107072984B (zh) * | 2014-07-15 | 2021-10-01 | 约翰·霍普金斯大学 | 源自骨髓的抑制细胞的抑制和免疫检查点阻断 |
| CA3116265A1 (en) | 2014-10-07 | 2016-04-14 | Cytlimic Inc. | Hsp70-derived peptide, pharmaceutical composition for treating or preventing cancer using same, immunity inducer, and method for producing antigen-presenting cell |
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| JP6898225B2 (ja) | 2015-03-09 | 2021-07-07 | サイトリミック株式会社 | Ｇｐｃ３由来のペプチド、これを用いた癌の治療又は予防のための医薬組成物、免疫誘導剤、及び抗原提示細胞の製造方法 |
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| CA2489076A1 (en) * | 2002-06-10 | 2003-12-18 | Avax Technologies Inc. | Cryopreservation of haptenized tumor cells |
| WO2005033278A2 (en) | 2003-09-30 | 2005-04-14 | Ludwig Institute For Cancer Research | In vivo efficacy of ny-eso-1 plus iscom |
| ES2322172T3 (es) * | 2004-05-26 | 2009-06-17 | Biovaxim Limited | Composiciones que comprenden agentes desmetilantes como potenciadores de la inmunoterapia para el tratamiento de infecciones cronicas y enfermedades neoplasicas y metodos para tratar las mismas. |
| BRPI0515735A2 (pt) | 2004-11-04 | 2011-10-11 | Pfizer Prod Inc | tratamento de combinação de anticorpo de ctla4 e inibidor de aromatase para cáncer de mama, suas composições farmacêuticas e respectivos usos |
| AU2005321898B2 (en) | 2004-12-29 | 2012-07-19 | Mannkind Corporation | Use of compositions comprising various tumor-associated antigens as anti-cancer vaccines |
| JP2008526976A (ja) * | 2005-01-14 | 2008-07-24 | アバクス・テクノロジーズ・インコーポレーテッド | 癌治療用ワクチンの製造方法 |
| EP2161336B2 (en) | 2005-05-09 | 2017-03-29 | ONO Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| AU2006265108C1 (en) | 2005-07-01 | 2013-01-17 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death ligand 1 (PD-L1) |
| EP1928492B1 (en) * | 2005-09-01 | 2011-02-23 | Celgene Corporation | Immunological uses of immunodulatory compounds for vaccine and anti-infections disease therapy |
| US7700567B2 (en) | 2005-09-29 | 2010-04-20 | Supergen, Inc. | Oligonucleotide analogues incorporating 5-aza-cytosine therein |
| US9744183B2 (en) * | 2009-07-06 | 2017-08-29 | Wave Life Sciences Ltd. | Nucleic acid prodrugs and methods of use thereof |
| SMT201700293T1 (it) * | 2009-07-20 | 2017-07-18 | Bristol Myers Squibb Co | Combinazione di un anticorpo anti-ctla-4 con etoposide per il trattamento sinergico di malattie proliferative |
| US20120277158A1 (en) * | 2009-10-06 | 2012-11-01 | Angiochem Inc. | Compositions and methods for the transport of therapeutic agents |
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| SG10201603034TA (en) * | 2011-04-15 | 2016-05-30 | Compugen Ltd | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
| EP2750768B1 (en) * | 2011-08-30 | 2018-10-03 | Astex Pharmaceuticals, Inc. | Decitabine derivative formulations |
| EP2958571B1 (en) * | 2013-02-21 | 2024-04-10 | Michele Maio | Dna hypomethylating agents for cancer therapy |
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