JP5015601B2 - 中枢神経系の癌を含む癌の処置のための系および方法 - Google Patents
中枢神経系の癌を含む癌の処置のための系および方法 Download PDFInfo
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Description
(1.発明の分野)
本発明は、癌の処置に関し、特定の実施形態においては、中枢神経系(「CNS」)の癌(例えば、脳において見出される癌)に関する。
悪性脳腫瘍は、最も重篤な形態の癌の1つである。これらの治癒不可能な腫瘍のうち最も一般的な多形性神経膠芽細胞腫(「GBM」)は、全ての頭蓋内神経膠腫のうちの50%、および成人における頭蓋内腫瘍の25%の原因である。例えば、非特許文献1および非特許文献2を参照のこと。GBMとの診断は、12ヶ月と18ヶ月との間の平均生存(90〜95%の患者が、2年未満しか生存しない)に繋がり、自発的な寛解の可能性も有効な処置の可能性もない。例えば、同書;および非特許文献3を参照のこと。GBMをこのような破滅的な疾患にせしめる、一貫して生存が短いことおよび自発的な寛解がないことはまた、この疾患に対する新規の治療法の評価を、比較的迅速かつ明確にする。腫瘍質量の減少(すなわち、外科的な減少)は、必ずしも生存の延長とは相関しないことに部分的に起因して、全体的な生存が、GBMに対する治療法が評価される基準を示す。例えば、非特許文献4;非特許文献5;および非特許文献6を参照のこと。
L.M.DeAngelis「Medical progress: Brain tumors」N.Engl.J.Med.,344:114(2001) F.G.Davisら「Prevalence estimates for primary brain tumors in the United States by behavior and major histology groups」Neuro−oncol.3:152(2001) W.J.J.Curranら「Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials」J.Natl.Cancer Inst.,85:690(1993) F.W.Krethら「Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme」J.Neurosurg.,78:762(1993) M.R.Quigleyら「Value of surgical intervention in the treatment of glioma」Stereotact.Funct.Neurosurg,65:171(1995) S.J.Hentschelら,「Current surgical management of glioblastoma」Cancer J.,9:113(2003) J.F.Reavey−Cantwellら「The prognostic value of tumor markers in patients with glioblastoma multiforme:analysis of 32 patients and review of the literature」J.Neurooncol.,55:195(2001) R.Stuppら「Recent developments in the management of malignant glioma」J.Clin.Oncol.,1091−9118:779(2001) H.A.Fineら「Meta−analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults」Cancer,71:2585(1993) S.Dieteら「Sex differences in length of survival with malignant astrocytoma, but not with glioblastoma」J.Neurooncol.,53:47(2001) R.P.Glickら「Intracerebral versus subcutaneous immunization with allogeneic fibroblasts genetically engineered to secrete interleukin−2 in the treatment of central nervous system glioma and melanoma」Neurosurg.,41:898(1997) L.M.Liauら「Treatment of intracranial gliomas with bone marrow−derived dendritic cells pulsed with tumor antigens」J.Neurosurg.,90:1115(1999) J.S.Yuら「Vaccination of malignant glioma patients with peptide−pulsed DC elicits systemic cytotoxicity and intracranial T−cell infiltration」Cancer Res.,61:842(2001) S.A.Rosenbergら「Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma」Nat.Med.,4:321(1998) K.H.Leeら「Increased vaccine−specific T cell frequency after peptide based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression」J.Immunol.,163:6292(1999) L.Fongら「Altered peptide ligand vaccination with Flt3 ligand expanded DC for tumor immunotherapy」Proc.Natl.Acad.Sci.USA,98:8809(2001) B.Bodeyら「Failure of cancer vaccines: the significant limitations of this approach to immunotherapy」Anticancer Res.,20:2665(2000)
本発明は、癌、特にCNSの癌(例えば、GBMのような脳の癌)の新規の処置に関する。一実施形態において、本発明は、少なくとも1種のDCワクチン接種、および少なくとも1種の化学療法の過程またはレジメンを含む、癌の処置に対する二重治療的アプローチを包含する。この2種の治療法は、互いに同時に投与されてもよいし、そして/または化学療法に先立って最初にワクチン接種が投与されてもよい。
本明細書中に引用される全ての参照は、完全に記載された通りに、参考として援用される。
(差次的に処置された患者間での比較)
新たに診断された新規GBM患者(GBMは、最初は低腫瘍度の神経膠腫の悪性疾患進行から生じなかった)を、3つのワクチン研究のうちの1つに登録させたか、または外科腫瘍切除および標準的放射線療法の後に、化学療法を単独で投与した。図5および図6において示されるように、ワクチン接種した(「ワクチン」または「ワクチン+化学療法」)患者に、自系腫瘍抗原で刺激したDCによる少なくとも3回のワクチン接種を行った。このワクチン接種は、それぞれ、手術後約15週間および放射線治療後5週間で開始した。化学療法単独を受けている患者(「化学療法」患者)を、図7において示すように、ワクチン接種患者と同じ時間間隔にわたって(手術、放射線、および化学療法で)処置した。連続MRIスキャンを、すべての患者において2〜3ヵ月ごとに実施した。ワクチン群、化学療法群、およびワクチン+化学療法群の間における腫瘍進行および全体的生存を、図1および図2において示されるように決定し比較した。
(GBM腫瘍の化学療法処置に対するワクチン接種の効果)
ワクチン接種がGBM腫瘍に対してより微細な影響を惹起し得たか否かを決定するために、本発明者らは、ワクチン接種がその後の化学療法に対するGBM感受性を変更し得るか否かを試験した。ワクチン接種後に化学療法を受けるGBM患者は、ワクチン接種単独を受けるGBM患者または化学療法単独を受けるGBM患者と比較して、有意に長期の腫瘍進行を享受した。同様に、ワクチン接種後に化学療法を受けるGBM患者は、いずれかの処置を個別に受けるGBM患者と比較して有意に長期の生存を示した。不注意な選択の偏向が、ワクチン接種後に化学療法を受ける患者において本質的に遅く進行する腫瘍をもたらす可能性は、3つすべての患者群(「ワクチン」、「化学療法」、および「ワクチン+化学療法」)の間で統計学的に同一である初期進行時間(すなわち、初期ワクチン接種後または初期化学療法後)と矛盾する。腫瘍は、初期ワクチン接種にも初期化学療法にも関わらず、臨床的に同じように挙動し、遅くなった腫瘍進行は、ワクチン接種後の化学療法期間に特有であった。さらに、2つ群のワクチン接種した患者は、他のすべての処置パラメーター(開頭術の数、放射線、SRS、およびワクチン接種前の化学療法)に関して統計学的に同一であり、ワクチン治療後に同様のKarnofsky活動(performance)スコアを示した。
(腫瘍進行時間の増加とのCD8+ TRECの相関性)
CD8+ T細胞の胸腺産生は、精製されたT細胞におけるTRECの濃度によって正確に反映される。例えば、D.C.Douekら「Assessment of thymic output in adults after haematopoietic stem−cell transplantation and prediciton of T−cell reconstitution」The Lancet 355:1875(2000);D.C.Douekら「Changes in thymic function with age and during the treatment of HIV infection」Nature 396:690(1998);およびB.D.Jamiesonら「Generation of functional thymocytes in the human adult」Immunity 10:569(1999)を参照のこと。さらに、CD8+ T細胞の胸腺産生は、年齢依存性神経膠腫の予後および結果の原因となり、そして主に、GBM患者におけるワクチン誘導性抗腫瘍応答に影響を与える。C.J.Wheelerら「Thymic CD8+ T cell production strongly influences tumor antigen recognition and age−dependent glioma mortality」J.Immunol.171(9):4927(2003)を参照のこと。本発明者らは、GBM化学感受性(これ自体は、年齢依存性の現象である(Fineら、2585頁を参照のこと))に対する抗腫瘍免疫の直接的影響は、同じGBM患者におけるCD8+ TRECと化学療法応答性との間の主要な関係によって反映されると推測した。従って、精製されたCD8+ T細胞におけるTREC含量は、ワクチン後の化学療法の後の腫瘍再発時間の増加と主に相関した。この関係は、化学感受性およびCD8+ T細胞の胸腺産生に対する、単なる年齢の独立的影響の関数ではなかった。なぜなら、この相関関係の強度および重要性は、ワクチン後の化学療法の後の再発時間の増加と患者の年齢との間の強度および重要度を上回ったからである(図4)。
(患者および臨床パラメーター)
すべての患者は、新たに診断されたGBMに罹患しており(平均55歳、32歳〜78歳の範囲)、処置および関連するモニタリングに対してインフォームド・コンセントを提供した。「ワクチン群」における患者には、開頭術を行った(5人の患者には、ワクチン治療を受ける前に1回の開頭術を行い、6人の患者には、2回の開頭術を行い、1人の患者には、ワクチン治療を受ける前に4回の開頭術を行った)。これらの患者すべてに、ワクチン接種前に一定治療期間の放射線を与えた。この群における4人の患者にはまた、化学療法を与え、1人の患者には、ワクチン接種前に定位放射線手術(「SRS」)を与えた。ワクチン接種後、これらの患者のうちの5人に、さらなる開頭術を行い、3人に、さらなる「SRS」を行った。ワクチン接種後には、誰にも化学療法を行わなかった。「化学療法群」におけるすべての患者には、開頭術、放射線、および化学療法を行った。これらの患者のうちの6人には、2回目の開頭術を行い、5人の患者には、さらなるSRSを行った。注目すべきことに、この群における全体的な最長生存者(991日間)は、手術後の頭蓋内膿瘍を患い、排膿のために複数回の外科手順を必要とした。悪性神経膠腫患者における頭蓋内感染が、長期生存と関連付けられており、抗腫瘍免疫応答を開始すると提唱された。A.P.J.Bowlesら「Long−term remission of malignant brain tumors after intracranial infections:a report of four cases」Neurosurgery 44:636(1999)を参照のこと。「ワクチンおよび化学療法群」における患者には、ワクチン治療を受ける前に開頭術を行った(8人の患者に、1回の開頭術を行い、5人の患者に、2回の開頭術を行った)。これらの患者すべては、放射線治療を行った。5人の患者には、さらなる化学療法を行い、3人の患者には、SRSを行った。ワクチン接種後に、これらの患者のうちの6人にさらなる開頭術を1回行い、5人にはSRSを行った。すべての患者には、腫瘍進行時にワクチン接種した後に化学療法を行った。顕著なことに、この群における1人の患者(>730日間生存した。図3Bに示す)は、ワクチン接種前に、DTH試験のために照射腫瘍細胞を接種した部位において、1つのリンパ節が改善した皮膚神経膠芽細胞腫を経験した。これらの2つの腫瘍を、化学療法の約1年間前に外科的に除去した。これらは再発しなかった。
(細胞の単離および溶解)
PBMCを、手術時に得た患者の血液および/または保存した白血球搬出物から、Ficollを用いて調製した。CD4+ T細胞およびCD8+ T細胞を、MACSビーズ分離(Miltenyi Biotec;Auburn,CAから得た)を使用して、PBMCから精製した。1ml当たり107個のCD4+細胞またはCD8+細胞を、100μg/mLプロテイナーゼK(Boehringer;Indianapolis,IN)中で56℃にて1時間溶解し、95℃にて10分間不活化することによって、定量的リアルタイムPCR(「qPCR」)のために調製した。
(TREC定量)
TRECを、D.C.Douekら「Assessment of thymic output in adults after haematopoietic stem−cell transplantaion and prediction of T−cell reconstitution」The Lancet 355:1875(2000)に記載されるように、5’ヌクレアーゼ(TaqMan)法を使用してqPCRによって二連または三連で定量し、iCymerシステム(BioRad;Hercules,CAから得た)上で検出した。TRECを、表1に示されるプライマー(プローブは、MegaBases;Chicago,ILから得た)を用いて、5μL細胞溶解物(50,000個の細胞由来)に対して実施した。
(統計分析)
統計分析は、疾患を有さない全体的生存についての両側マン−ホイットニーlogランク検定と、二項分布確率と、SASおよびExcelソフトウェアを用いて計算したピアゾン相関係数(r値)とを含んだ。二項分布を、ワクチン+化学療法患者群と、他の(ワクチンまたは化学療法)患者群との間の2年生存頻度および3年生存頻度について、決定した。
Claims (24)
- 哺乳動物における神経膠腫を処置するための組み合わせ物であって、該組み合わせ物は、以下:
少なくとも1つの樹状細胞(DC)ワクチンであって、ここで、該DCは、自系腫瘍抗原が提示されたDCであり、ここで、該腫瘍が神経膠腫である、ワクチン;および、
少なくとも1種の化学療法剤、
を含み;
ここで、該少なくとも1つのDCワクチンは、該少なくとも1種の化学療法剤を投与する前に投与するために適切である、組み合わせ物。 - 請求項1に記載の組み合わせ物であって、前記DCは、エキソビボで刺激される、組み合わせ物。
- 請求項1に記載の組み合わせ物であって、前記少なくとも1つのDCワクチンは、少なくとも3つのDCワクチンを含む、組み合わせ物。
- 請求項1に記載の組み合わせ物であって、前記少なくとも1つのDCワクチンの各々は、105個〜107個のDCを含む、組み合わせ物。
- 請求項1に記載の組み合わせ物であって、前記少なくとも1つのDCワクチンの各々は、10×106個〜40×106個のDCを含む、組み合わせ物。
- 請求項1に記載の組み合わせ物であって、前記少なくとも1種の化学療法剤は、テモゾロミド、プロカルバジン、カルボプラチン、ビンクリスチン、BCNU、CCNU、サリドマイド、イリノテカン、イソトレチノイン、イマチニブ、エトポシド、およびこれらの組み合わせからなる群より選択される、組み合わせ物。
- 請求項1に記載の組み合わせ物であって、前記神経膠腫は、多形性神経膠芽細胞腫である、組み合わせ物。
- 哺乳動物の化学感受性を増加させるための組成物であって、該組成物は、
少なくとも1つの樹状細胞(「DC」)ワクチンであって、ここで、該DCは、自系腫瘍抗原が提示されたDCであり、ここで、該腫瘍が神経膠腫である、ワクチン
を含み;
該哺乳動物の化学感受性は、神経膠腫の化学療法処置に関して増加され;
該少なくとも1つのDCワクチンは、該化学療法処置の前に投与するために適切である、組成物。 - 請求項8に記載の組成物であって、前記DCは、エキソビボで刺激される、組成物。
- 請求項8に記載の組成物であって、前記少なくとも1つのDCワクチンは、少なくとも3つのDCワクチンを含む、組成物。
- 請求項8に記載の組成物であって、前記少なくとも1つのDCワクチンの各々は、105個〜107個のDCを含む、組成物。
- 請求項8に記載の組成物であって、前記少なくとも1つのDCワクチンの各々は、10×106個〜40×106個のDCを含む、組成物。
- 請求項8に記載の組成物であって、前記哺乳動物の化学感受性は、多形性神経膠芽細胞腫の化学療法処置に関して増加される、組成物。
- 神経膠腫の処置における使用のためのキットであって、該キットは、
一定量の樹状細胞(「DC」)であって、ここで、該DCは、自系腫瘍抗原が提示されたDCであり、ここで、該腫瘍が神経膠腫である、DC;
一定量の少なくとも1種の化学療法剤;および
該神経膠腫の処置において該一定量の少なくとも1種の化学療法剤に先立って該一定量のDCを使用するための指示書;
とを備える、キット。 - 請求項14に記載のキットであって、前記神経膠腫は、多形性神経膠芽細胞腫である、キット。
- 請求項14に記載のキットであって、一定量のDCをエキソビボで刺激する際に使用するための少なくとも1種の成分をさらに備える、キット。
- 請求項14に記載のキットであって、前記一定量のDCは、エキソビボで刺激される、キット。
- 請求項14に記載のキットであって、前記一定量のDCは、少なくとも1つのDCワクチンで投与するために適切である、キット。
- 請求項18に記載のキットであって、前記少なくとも1つのDCワクチンは、少なくとも3つのDCワクチンを含む、キット。
- 請求項18に記載のキットであって、前記少なくとも1つのDCワクチンの各々は、105個〜107個のDCを含む、キット。
- 請求項18に記載のキットであって、前記少なくとも1つのDCワクチンの各々は、10×106個〜40×106個のDCを含む、キット。
- 請求項14に記載のキットであって、前記少なくとも1種の化学療法剤が、テモゾロミド、プロカルバジン、カルボプラチン、ビンクリスチン、BCNU、CCNU、サリドマイド、イリノテカン、イソトレチノイン、イマチニブ、エトポシド、およびこれらの組み合わせからなる群より選択される、キット。
- 哺乳動物における神経膠腫を処置するための組成物であって、該組成物は、以下:
少なくとも1つの化学療法剤;
を含み;
ここで、該少なくとも1つの化学療法剤は、少なくとも1つの樹状細胞(DC)ワクチンの投与後に投与されるのに適しており、ここで、該DCは、自系腫瘍抗原が提示されたDCであり、ここで、該腫瘍が神経膠腫である、組成物。 - 請求項23に記載の組成物であって、前記少なくとも1つの化学療法剤が、テモゾロミド、プロカルバジン、カルボプラチン、ビンクリスチン、BCNU、CCNU、サリドマイド、イリノテカン、イソトレチノイン、イマチニブ、エトポシド、およびこれらの組み合わせからなる群より選択される、組成物。
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Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AUPQ801700A0 (en) * | 2000-06-07 | 2000-06-29 | Peplin Research Pty Ltd | Enzyme and viral activation |
WO2005037995A2 (en) * | 2003-10-06 | 2005-04-28 | Cedars-Sinai Medical Center | Use of cox-2 inhibitor to prevent t-cell anergy induced by dendritic cell therapy |
US8106092B2 (en) * | 2004-12-13 | 2012-01-31 | Leo Laboratories Limited | Treatment of solid cancers |
US7705010B2 (en) | 2005-02-22 | 2010-04-27 | Cedars-Sinai Medical Center | Use of minoxidil sulfate as an anti-tumor drug |
GB0519303D0 (en) * | 2005-09-21 | 2005-11-02 | Oxford Biomedica Ltd | Chemo-immunotherapy method |
KR101399591B1 (ko) | 2005-11-02 | 2014-06-18 | 더 보드 오브 리전츠 오브 더 유니버시티 오브 텍사스 시스템 | 동시 화학요법 및 면역요법 |
WO2007059584A1 (en) * | 2005-11-25 | 2007-05-31 | Peplin Research Pty Ltd | Methods for wound healing |
CA2700573C (en) | 2006-09-26 | 2016-11-22 | Cedars-Sinai Medical Center | Cancer stem cell antigen vaccines and methods |
WO2008039969A2 (en) | 2006-09-28 | 2008-04-03 | Cedars-Sinai Medical Center | Cancer vaccines and vaccination methods |
EP2313506A1 (en) * | 2008-07-11 | 2011-04-27 | Medizinische Universität Innsbruck | Antagonists of nr2f6 for augmenting the immune response |
EP2328923B1 (en) | 2008-09-02 | 2016-01-13 | Cedars-Sinai Medical Center | Cd133 epitopes |
US8728806B2 (en) * | 2008-12-06 | 2014-05-20 | The Board Of Regents, The University Of Texas System | Methods and compositions related to Th-1 dendritic cells |
US9067005B2 (en) | 2008-12-08 | 2015-06-30 | Thoratec Corporation | Centrifugal pump apparatus |
PT2427485T (pt) | 2009-05-07 | 2017-03-13 | Immunocellular Therapeutics Ltd | Epitopos cd133 |
WO2013112881A1 (en) | 2012-01-27 | 2013-08-01 | Thomas Jefferson University | Mct protein inhibitor-related prognostic and therapeutic methods |
US10137182B2 (en) | 2013-02-14 | 2018-11-27 | Immunocellular Therapeutics, Ltd. | Cancer vaccines and vaccination methods |
WO2014172627A1 (en) * | 2013-04-19 | 2014-10-23 | Thomas Jefferson University | Caveolin-1 related methods for treating glioblastoma with temozolomide |
KR20200047660A (ko) | 2017-09-01 | 2020-05-07 | 다나-파버 캔서 인스티튜트 인크. | 암의 치료를 위한 bcma 및 taci 항원에 특이적인 면역원성 펩타이드 |
Family Cites Families (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
US6037135A (en) * | 1992-08-07 | 2000-03-14 | Epimmune Inc. | Methods for making HLA binding peptides and their uses |
DK0633929T3 (da) * | 1992-04-01 | 2004-06-28 | Univ Rockefeller | Fremgangsmåde til in vitro proliferation af dendritcelleforstadier og deres anvendelse til at producere immunogener |
US6077519A (en) * | 1993-01-29 | 2000-06-20 | University Of Pittsburgh | Methods for isolation and use of T cell epitopes eluted from viable cells in vaccines for treating cancer patients |
US5419900A (en) | 1993-05-19 | 1995-05-30 | The United States Of America As Represented By The Department Of Of Health And Human Services | Immunologic enhancement with intermittent interleukin-2 therapy |
US5550214A (en) | 1994-02-10 | 1996-08-27 | Brigham And Women's Hospital | Isolated antigenic oncogene peptide fragments and uses |
JPH10505481A (ja) * | 1994-04-22 | 1998-06-02 | アメリカ合衆国 | メラノーマ抗原 |
EP0793501A4 (en) | 1994-12-14 | 2000-05-03 | Scripps Research Inst | IN VIVO ACTIVATION OF TUMOR SPECIFIC CYTOTOXIC T CELLS |
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 |
US6010905A (en) * | 1995-01-27 | 2000-01-04 | The United States Of America As Represented By The Department Of Health & Human Services | Method for inducing monocytes to exhibit the phenotype of activated myeloid dendritic cells |
US6514942B1 (en) * | 1995-03-14 | 2003-02-04 | The Board Of Regents, The University Of Texas System | Methods and compositions for stimulating T-lymphocytes |
US5788963A (en) * | 1995-07-31 | 1998-08-04 | Pacific Northwest Cancer Foundation | Isolation and/or preservation of dendritic cells for prostate cancer immunotherapy |
US5849589A (en) * | 1996-03-11 | 1998-12-15 | Duke University | Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells |
US6458585B1 (en) * | 1996-08-14 | 2002-10-01 | Nexell Therapeutics Inc. | Cytokine-free culture of dendritic cells |
EP0983345A1 (en) * | 1997-05-21 | 2000-03-08 | THE UNITED STATES OF AMERICA, as represented by the Secretary of the Department of Health and Human Services | Methods and compositions for making dendritic cells from expanded populations of monocytes and for activating t cells |
US6565831B1 (en) * | 1999-02-24 | 2003-05-20 | Oncolytics Biotech Inc. | Methods for preventing reovirus recognition for the treatment of cellular proliferative disorders |
US20020034819A1 (en) * | 1998-02-23 | 2002-03-21 | Alan K. Smith | Human lineage committed cell composition with enhanced proliferative potential, biological effector function, or both; methods for obtaining same; and their uses |
US20020192211A1 (en) * | 1998-03-17 | 2002-12-19 | Hudziak Robert M. | Method of treating tumor cells by inhibiting growth factor receptor function |
JP4768916B2 (ja) * | 1998-09-15 | 2011-09-07 | ユニバーシティ オブ ピッツバーグ オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション | サイトカイン発現が遺伝的に増強された抗原提示細胞のインサイチュ注入 |
AU1598500A (en) | 1998-10-26 | 2000-05-15 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Hla-a2 and hla-dr specific peptide epitopes from the melanoma antigen trp2 |
GB9824306D0 (en) * | 1998-11-05 | 1998-12-30 | Isis Innovation | Method for producing dendritic dells |
DE69930764D1 (de) | 1998-12-23 | 2006-05-18 | G D Searle Llc St Louis | Verwendung von cyclooxygenase-2 inhibitor celecoxib und capecitabine zur kombinationsbehandlung von neoplasia |
US6566395B1 (en) * | 1999-05-25 | 2003-05-20 | Biomedicines, Inc. | Methods of treating proliferative disorders |
US7060284B1 (en) | 1999-08-03 | 2006-06-13 | The Ohio State University | Polypeptides and polynucleotides for enhancing immune reactivity to HER-2 protein |
US20070098776A1 (en) * | 1999-12-13 | 2007-05-03 | Fikes John D | HLA class I A2 tumor associated antigen peptides and vaccine compositions |
AU2273701A (en) | 1999-12-13 | 2001-06-18 | Epimmune, Inc. | Hla class i a2 tumor associated antigen peptides and vaccine compositions |
JP2004511425A (ja) * | 2000-02-08 | 2004-04-15 | ザ ペン ステート リサーチ ファウンデーション | 免疫療法に使用されるインターロイキン13受容体サブユニットアルファー2 |
AU2001288863A1 (en) * | 2000-09-15 | 2002-03-26 | Ortho-Mcneil Pharmaceutical, Inc. | Compositions and methods for inducing specific cytolytic t cell responses |
US20030202963A1 (en) * | 2000-10-12 | 2003-10-30 | Cornell Research Foundation, Inc. | Method of treating cancer |
US6632459B2 (en) * | 2000-12-11 | 2003-10-14 | Nutricia N.V. | Chlorogenic acid and an analog thereof for immune system stimulation |
EP1236740B1 (de) | 2001-02-28 | 2012-07-18 | Bio Life Science Forschungs- und Entwicklungsges.m.b.H. | Vakzine gegen Krebserkrankungen, die mit dem HER-2/neu Onkogen assoziiert sind |
DE10132502A1 (de) * | 2001-07-05 | 2003-01-23 | Gsf Forschungszentrum Umwelt | Angriff auf Tumorzellen mit fehlender, niedriger oder anormaler MHC-Expression durch kombinieren von nicht MHC-Restringierten T-Zellen/NK-Zellen und MHC-Restringierten Zellen |
WO2003010301A1 (en) * | 2001-07-25 | 2003-02-06 | I.D.M. Immuno-Designed Molecules | New isolated dendritic cells, a process for preparing the same and their use in pharmaceutical compositions |
GB0119346D0 (en) | 2001-08-08 | 2001-10-03 | Bioclones Proprietary Ltd | Process for the maturation of dendritic cells |
US7763243B2 (en) * | 2001-08-17 | 2010-07-27 | Roger Williams Medical Center | In situ immunization |
KR101803702B1 (ko) * | 2001-09-06 | 2017-12-01 | 노쓰웨스트 바이오써라퓨틱스, 인크. | Th-1 반응을 위한 단구성 수지상 세포 및 T 세포를 프라이밍하기 위한 조성물 및 방법 |
US20040072246A1 (en) * | 2001-09-11 | 2004-04-15 | Roland Martin | System and method for identifying t cell and other epitopes and the like |
EP1446159A4 (en) | 2001-10-26 | 2005-06-01 | Irx Therapeutics Inc | IMMUNOTHERAPY FOR REVERSING AN IMMUNE UPPRESSION |
US7413869B2 (en) * | 2002-04-05 | 2008-08-19 | Dendreon Corporation | Method for determining potency of antigenic presenting cell based vaccines |
US20040057935A1 (en) * | 2002-09-20 | 2004-03-25 | Cedars-Sinai Medical Center | Intratumoral delivery of dendritic cells |
US20040197903A1 (en) * | 2003-01-31 | 2004-10-07 | Northwest Biotherapeutics, Inc. | Method for induction of proliferation of natural killer cells by dendritic cells cultured with GM-CSF and IL-15 |
TW200506061A (en) * | 2003-02-27 | 2005-02-16 | Northwest Biotherapeutics Inc | Generation of dendritic cells from monocytic dendritic precursor cells with gm-csf in the absence of additional cytokines |
WO2005037995A2 (en) | 2003-10-06 | 2005-04-28 | Cedars-Sinai Medical Center | Use of cox-2 inhibitor to prevent t-cell anergy induced by dendritic cell therapy |
WO2005079581A1 (en) | 2004-01-20 | 2005-09-01 | Cedars-Sinai Medical Center | Intratumoral delivery of dendritic cells |
WO2006034334A2 (en) * | 2004-09-21 | 2006-03-30 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Peptide analogs capable of enhancing stimulation of a glioma-specific ctl response |
WO2006099448A2 (en) * | 2005-03-14 | 2006-09-21 | University Of Iowa Research Foundation | Accelerated cd8+ t-cell memory after dendritic cell vaccination |
US20080107668A1 (en) * | 2006-08-30 | 2008-05-08 | Immunotope, Inc. | Cytotoxic t-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
CA2700573C (en) | 2006-09-26 | 2016-11-22 | Cedars-Sinai Medical Center | Cancer stem cell antigen vaccines and methods |
WO2008039969A2 (en) | 2006-09-28 | 2008-04-03 | Cedars-Sinai Medical Center | Cancer vaccines and vaccination methods |
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EP1676132A1 (en) | 2006-07-05 |
JP2007509156A (ja) | 2007-04-12 |
US7939090B2 (en) | 2011-05-10 |
JP2010132684A (ja) | 2010-06-17 |
EP1676132B1 (en) | 2014-01-22 |
EP1676132A4 (en) | 2007-05-09 |
WO2005043155A1 (en) | 2005-05-12 |
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