JP2018532810A - がんの処置のための腫瘍抑制因子遺伝子治療および免疫チェックポイント治療を含む組成物 - Google Patents
がんの処置のための腫瘍抑制因子遺伝子治療および免疫チェックポイント治療を含む組成物 Download PDFInfo
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Abstract
Description
3KB(Microsoft Windows(登録商標)で測定される場合)であり、2016年11月7日作成のファイル名「SOBLP0143WO_ST25.txt」に含まれる配列表は、電子提出によって本明細書とともに出願され、かつ本明細書に参考として援用される。
1.発明の分野
本発明は、一般に、生物学および医療の分野に関する。より具体的には、本発明は、免疫チェックポイントインヒビターの有効性および腫瘍抑制遺伝子の発現を併用する方法および組成物に関する。
悪性細胞は、頻繁に、DNA損傷因子(例えば、化学療法および放射線誘導性のプログラムされた細胞死またはアポトーシス)に抵抗性である。このような抵抗性は一般に、ある特定のがん遺伝子の異常発現またはアポトーシスの制御における腫瘍抑制遺伝子の発現の喪失の結果である。欠損している腫瘍抑制遺伝子に置き換わる、およびアポトーシス誘導遺伝子の発現を押し進めるように設計されたストラテジーは、腫瘍細胞における細胞死のこの様式を回復させるために有望である。
一実施形態において、本発明は、被験体においてがんを処置するための方法および組成物を提供し、上記方法は、(a)上記被験体に、p53をコードする核酸および/またはMDA−7をコードする核酸の有効量を投与する工程;ならびに(b)少なくとも1種の免疫チェックポイントインヒビターを投与する工程を包含する。ある特定の局面において、1種より多くのチェックポイントインヒビターが投与される。特定の局面において、上記被験体はヒトである。
腫瘍がその始まりおよび進行の間に進化して、免疫系による破壊から逃れることは周知である。この抵抗性を改善するために免疫チェックポイントインヒビターを近年使用することで、ある種の成功が示された一方で、患者の大部分は、これらの処置に応答しない。本発明は、腫瘍の微小環境を変化させて、抵抗性を克服するおよび抗腫瘍免疫応答を増強するための方法および組成物を提供することによって、現在の技術と関連する難題を克服する。一実施形態において、p53および/またはMDA−7を、少なくとも1種の免疫チェックポイントインヒビターと組み合わせて発現することによる、がんの処置のための方法が提供される。特に、腫瘍抑制遺伝子は、複製不能アデノウイルスとして投与される。一方法において、p53遺伝子治療は、適応抗腫瘍免疫応答を誘導するために、免疫チェックポイントインヒビター(例えば、抗PD−1抗体)と併用してMDA−7遺伝子治療を投与する前に、先天性抗腫瘍免疫を増強するために、免疫チェックポイントインヒビター(例えば、抗PD1抗体または抗KIR抗体)と併用して投与される。あるいは、p53およびMDA−7は、免疫チェックポイントインヒビターと同時に投与され得る。
本明細書で使用される場合、特定された構成要素に関して「本質的に含まない(essentially free)」とは、その特定された構成要素が組成物へと故意に製剤化されていない、および/または汚染物質としてもしくは微量においてのみ存在することを意味するために、本明細書で使用される。組成物の何らかの意図されない汚染から生じるその特定された構成要素の総量は、従って、0.05%を十分に下回り、好ましくは0.01%を下回る。最も好ましいのは、その特定された構成要素の量が標準的分析法で全く検出できない組成物である。
A. p53
本発明は、がんの処置のための併用療法を提供する。本明細書で提供される併用療法のうちのいくつかは、野生型p53遺伝子を被験体に投与する工程を包含する、p53遺伝子治療を含む。野生型p53は、多くの細胞タイプにおいて重要な増殖調節因子として認識される。p53遺伝子は、宿主タンパク質(例えば、ラージT抗原およびE1B)と複合体を形成し得る375アミノ酸のリンタンパク質をコードする。そのタンパク質は、正常な組織および細胞において見出されるが、その濃度は、形質転換された細胞または腫瘍組織と比較するとわずかである。
本明細書で提供される併用療法はまた、全長または短縮化MDA−7遺伝子を投与する工程を包含するMDA−7遺伝子治療をさらに含み得る。mda−7遺伝子のタンパク質生成物、インターロイキン(IL)−24は、サイトカインのIL−10ファミリーに属するサイトカインであり、腫瘍抑制因子でもある。MDA−7タンパク質をコードするcDNAは、Jiangら, 1995(WO1995011986)によって記載されている。MDA−7 cDNAは、推定サイズ23.8kDaを有する206アミノ酸の進化の過程で保存されたタンパク質をコードする。
腫瘍抑制遺伝子治療および/または免疫チェックポイントインヒビターの抗腫瘍効果を増強するための方法がまた、本明細書で提供される。一局面において、遺伝子治療の送達(例えば、ウイルス分配)および腫瘍浸透は、腫瘍細胞細胞外マトリクス(ECM)またはその構成要素を分解するタンパク質または薬剤によって増強される。
本明細書で提供される方法において使用され得る1つの細胞外マトリクス分解タンパク質は、リラキシンである。リラキシンは、インスリンおよびインスリン様増殖因子に構造的に関連する6kDaのペプチドホルモンである。リラキシンは、黄体および子宮内膜において主に生成され、その血清レベルは、妊娠中に大きく増大する(Sherwoodら, 1984)。リラキシンは、コラーゲンが過剰発現される場合に、コラーゲン発現の強力なインヒビターであるが、他のコラーゲンとは対照的に、コラーゲン発現の基底レベルを顕著に変化させない。それは、種々のMMP(例えば、MMP2、MMP3、およびMMP9)の発現を促進して、コラーゲンを分解するので、結合組織および基底膜は、産道の細胞外マトリクスの破壊をもたらすように分解される。このことに加えて、リラキシンによるMMP 1およびMMP 3発現の促進はまた、リラキシンがインヒビターとして役割を果たしてコラーゲンの過剰発現を防止する場所である肺、心臓、皮膚、腸、乳腺、血管および精管において観察される。(Qin, X.,ら, 1997a; Qin, X.,ら, 1997b)。
いくつかの実施形態において、細胞外マトリクスの中に一般に存在するポリサッカリド(例えば、ヒアルロン酸)を加水分解し得る任意の物質が、投与され得る。特に、本発明において使用される細胞外マトリクス分解タンパク質は、ヒアルロニダーゼであり得る。ヒアルロナン(またはヒアルロン酸)は、脊椎動物細胞外マトリクスの遍在する成分である。この直線状のポリサッカリドは、グルクロン酸およびグルコサミン[D−グルクロン酸 1−β−3)N−アセチル−D−グルコサミン(1−b−4)]に基づき、非常に粘性の溶液を形成するその特性によって、マトリクスの物理化学的特徴に対して影響を発揮し得る。ヒアルロン酸はまた、細胞の表面に位置する種々のレセプターおよび結合タンパク質と相互作用する。ヒアルロン酸は、非常に多くの生物学的プロセス(例えば、受精、胚発生、細胞移動および分化、創傷治癒、炎症、腫瘍増殖および転移の形成)に関与する。
デコリン(小さなロイシンリッチプロテオグリカン)は、細胞外マトリクスの遍在する構成要素であり、コラーゲン原線維(collagen fibril)に関連して優先的に見出される。デコリンは、コラーゲン原線維に結合し、個々の3本鎖らせんのコラーゲン分子の側方アセンブリ(lateral assembly)を遅らせ、原線維の直径の低下を生じる。さらに、デコリンは、細胞外マトリクス構成要素(例えば、フィブロネクチンおよびトロンボスポンディン)の、細胞との相互作用を調節し得る。さらに、デコリンは、マトリクスメタロプロテイナーゼであるコラゲナーゼの誘導によって細胞外マトリクスリモデリングに影響を及ぼし得る。これらの観察は、デコリンが、細胞外マトリクスの生成およびアセンブリをいくつかのレベルで調節するので、Choiら(Gene Therapy, 17: 190−201, 2010)およびXuら (Gene Therapy, 22(3) : 31−40, 2015)によって記載されるように結合組織をリモデリングするにあたって顕著な役割を有することを示唆する。
核酸は、当業者に公知の任意の技術によって作製され得る。合成核酸、特に、合成オリゴヌクレオチドの非限定的な例としては、ホスホトリエステル、ホスファイトまたはホスホルアミダイト化学および固相技術(例えば、EP 266,032に記載されるとおり)を使用するか、またはFroehlerら, 1986、および米国特許第5,705,629号に記載されるようにデオキシヌクレオシドH−ホスホネート中間体を介してインビトロ化学合成によって作製される核酸が挙げられる。酵素によって生成される核酸の非限定的な例としては、PCRTM(例えば、米国特許第4,683,202号および米国特許第4,682,195号を参照のこと)のような増幅反応における酵素によって、または米国特許第5,645,897号に記載されるオリゴヌクレオチドの合成によって生成されるものが挙げられる。生物学的に生成される核酸の非限定的な例としては、生細胞における組換え核酸生成(例えば、細菌中での組換えDNAベクター生成(例えば、Sambrookら 1989を参照のこと)が挙げられる。
本明細書で提供されるベクターは主に、調節された真核生物プロモーター(すなわち、構成性、誘導性、抑制性、組織特異的)の制御下で治療用腫瘍抑制遺伝子(例えば、p53および/またはMDA−7)および/または細胞外マトリクス分解性遺伝子(例えば、リラキシン)を発現するように設計される。いくつかの局面において、p53およびMDA−7は、ベクターにおいて共発現され得る。別の局面において、p53および/またはMDA−7は、細胞外マトリクス分解性遺伝子と共発現され得る。また、そのベクターは、他の理由がなくても、インビトロでのそれらの取り扱いを容易にするために、選択マーカーを含み得る。
腫瘍抑制因子および/または細胞外マトリクス分解性遺伝子をコードするウイルスベクターは、本発明のある特定の局面において提供され得る。組換えウイルスベクターを生成するにあたって、非必須遺伝子は、代表的には、異種(または非天然)タンパク質の遺伝子またはコード配列で置き換えられる。ウイルスベクターは、ウイルス配列を利用して、核酸およびおそらくタンパク質を細胞に導入するある種の発現構築物である。ある特定のウイルスが細胞に感染するかまたはレセプター媒介性エンドサイトーシスを介して細胞に侵入し、宿主細胞ゲノムへと組み込まれ、ウイルス遺伝子を安定してかつ効率的に発現する能力は、そのウイルスを、外来核酸を細胞(例えば、哺乳動物細胞)へと移入するための魅力的な候補にしている。本発明のある特定の局面の核酸を送達するために使用され得るウイルスベクターの非限定的な例は、以下に記載される。
腫瘍抑制因子および/または細胞外マトリクス分解性遺伝子の送達のための1方法は、アデノウイルス発現ベクターの使用を要する。アデノウイルスベクターは、ゲノムDNAの組み込みのためには低い収容力を有することが公知であるが、この特徴は、これらのベクターによって提供される遺伝子移入の高い効率で相殺される。アデノウイルス発現ベクターは、(a)構築物のパッケージングを支援する、および(b)その中にクローニングされた組換え遺伝子構築物を最終的に発現させる、ために十分なアデノウイルス配列を含む構築物を含む。
さらに、腫瘍抑制因子および/または細胞外マトリクス分解性遺伝子は、レトロウイルスベクターによってコードされ得る。レトロウイルスは、それらのRNAを、逆転写プロセスによって感染細胞において2本鎖DNAへと変換する能力によって特徴付けられる1本鎖RNAウイルスの群である(Coffin, 1990)。得られたDNAは、次いで、プロウイルスとして細胞染色体へと安定して組み込まれ、ウイルスタンパク質の合成を指向する。その組み込みは、レシピエント細胞およびその子孫においてウイルス遺伝子配列の保持を生じる。レトロウイルスゲノムは、キャプシドタンパク質、ポリメラーゼ酵素、およびエンベロープ構成要素をそれぞれコードする、3種の遺伝子、gag、pol、およびenvを含む。gag遺伝子から上流で見出された配列は、ゲノムをビリオンへとパッケージングするためのシグナルを含む。2つの長末端反復(LTR)配列は、ウイルスゲノムの5’末端および3’末端に存在する。これらは、強力なプロモーターおよびエンハンサー配列を含み、宿主細胞ゲノムにおける組み込みにも必要とされる(Coffin, 1990)。
アデノ随伴ウイルス(AAV)は、本開示における使用に魅力的なベクター系である。なぜならそれは、高い組み込み頻度を有しかつ分裂していない細胞に感染し得るので、このことがアデノ随伴ウイルスベクターを哺乳動物細胞への遺伝子の送達に有用にするからである(Muzyczka, 1992)。AAVは、感染性に関して広い宿主範囲を有する(Tratschin,ら, 1984; Laughlin,ら, 1986; Lebkowski,ら, 1988; McLaughlin,ら, 1988)。このことは、本発明での使用に適用可能であることを意味する。rAAVベクターの生成および使用に関する詳細は、米国特許第5,139,941号および米国特許第4,797,368号に記載される。
他のウイルスベクターは、本開示において構築物として使用され得る。ワクシニアウイルス(Ridgeway, 1988; Baichwal and Sugden, 1986; Couparら, 1988)およびヘルペスウイルスのようなウイルスに由来するベクターが使用され得る。それらは、種々の哺乳動物細胞にとって魅力的ないくつかの特徴を提供する(Friedmann, 1989; Ridgeway, 1988; Baichwal and Sugden, 1986; Couparら, 1988; Horwichら, 1990)。
本開示において有用なベクターに含まれる発現カセットは、特に、(5’から3’方向に)真核生物転写プロモーター、(これに作動可能に連結された)タンパク質コード配列、介在配列を含むスプライスシグナル、および転写終結/ポリアデニル化配列を含む。真核生物においてタンパク質コード遺伝子の転写を制御するプロモーターおよびエンハンサーは、複数の遺伝的エレメントから構成される。その細胞機構は、各エレメントによって伝えられる調節情報を集めかつ統合し得、種々の遺伝子が、転写調節の別個の、しばしば複雑なパターンを進化させることを可能にし得る。本発明の状況で使用されるプロモーターは、構成性、誘導性、および組織特異的なプロモーターを含む。
本明細書で提供される発現構築物は、腫瘍抑制因子および/または細胞外マトリクス分解性遺伝子の発現を駆動するプロモーターを含む。プロモーターは、一般に、RNA合成のための出発部位を配置するように機能する配列を含む。このもっともよく知られた例は、TATAボックスであるが、TATAボックスを欠くいくつかのプロモーター(例えば、哺乳動物末端デオキシヌクレオチジルトランスフェラーゼ遺伝子のためのプロモーターおよびSV40後期遺伝子のためのプロモーターのような)では、その開始部位自体に重なる別個のエレメントが、開始の場所を固定するために役立つ。さらなるプロモーターエレメントは、転写開始の頻度を調節する。代表的には、これらは、開始部位の30〜110bp上流の領域に位置するが、多くのプロモーターは、開始部位の下流にある機能的エレメントを含むことも示された。コード配列をプロモーター「の制御下に」置くために、その選択されたプロモーターの「下流」に(すなわち、3’側に)にある転写リーディングフレームの転写開始部位の5’末端に配置される。「上流」プロモーターは、DNAの転写を刺激し、そのコードされたRNAの発現を促進する。
特異的開始シグナルはまた、コード配列の効率的翻訳のために本開示で提供される発現構築物において使用され得る。これらのシグナルは、ATG開始コドンまたは隣接する配列を含む。外因性の翻訳制御シグナル(ATG開始コドンを含む)は、提供される必要があり得る。当業者は容易に、これを決定しかつ必要なシグナルを提供し得る。挿入物全体の翻訳を担保するために、開始コドンが所望のコード配列のリーディングフレームと「インフレーム」でなければならないことは周知である。外因性の翻訳制御シグナルおよび開始コドンは、天然または合成のいずれかであり得る。発現効率は、適切な転写エンハンサーエレメントを含めることによって増強され得る。
宿主細胞においてベクターを増殖させるために、ベクターは、1もしくはこれより多くの複製起点部位(しばしば「ori」といわれる)、例えば、上記で記載されるとおりのEBVのoriPまたは遺伝子操作された、プログラミングにおいて類似もしくは高められた機能を有するoriPに相当する核酸配列を含み得る。この配列は、複製が開始される特異的核酸配列である。あるいは、上記に記載されるとおりの他の染色体外複製ウイルスの複製起点または自律複製配列(ARS)が使用され得る。
いくつかの実施形態において、本開示の構築物を含む細胞は、発現ベクターの中にマーカーを含めることによって、インビトロまたはインビボで同定され得る。このようなマーカーは、同定可能な変化を細胞に付与し、発現ベクターを含む細胞の容易な同定を可能にする。一般に、選択マーカーは、選択を可能にする特性を付与するものである。陽性選択マーカーは、マーカーの存在がその選択を可能にするものである一方で、陰性選択マーカーは、その存在がその選択を防止するものである。陽性選択マーカーの例は、薬物耐性マーカーである。
腫瘍抑制因子および/または細胞外マトリクス分解性遺伝子をコードする核酸のウイルス送達に加えて、以下は、所定の宿主細胞への組換え遺伝子送達のさらなる方法であるので、本開示において考慮される。
本開示のある特定の具体的実施形態において、遺伝子構築物は、エレクトロポレーションを介して標的の過剰増殖性細胞へと導入される。エレクトロポレーションは、細胞(または組織)およびDNA(またはDNA複合体)を高電圧放電へと曝すことを要する。
さらなる実施形態において、腫瘍抑制因子および/または細胞外マトリクス分解性遺伝子は、リポソームまたは脂質製剤中に捕捉され得る。リポソームは、リン脂質二重層膜および内側の水性媒体によって特徴付けられる小胞構造である。マルチラメラリポソームは、水性媒体によって分離された複数の脂質層を有する。それらは、リン脂質が過剰の水性溶液中で懸濁される場合に自発的に形成する。脂質構成要素は、閉じた構造を形成する前に自己再編成を受け、水および溶解した溶質を脂質二重層の間に捕捉する(Ghosh and Bachhawat, 1991)。Lipofectamine(Gibco BRL)と複合体化した遺伝子構築物も企図される。
本開示は、免疫チェックポイントの遮断と腫瘍抑制遺伝子治療(例えば、p53および/またはMDA−7遺伝子治療)とを併用する方法を提供する。免疫チェックポインは、シグナル(例えば、共刺激分子)を上昇させるかまたはシグナルを低下させるかのいずれかである免疫系の分子である。免疫チェックポイント遮断によって標的化され得る阻害性チェックポイント分子としては、アデノシンA2Aレセプター(A2AR)、B7−H3(CD276としても公知)、BおよびTリンパ球減衰因子(B and T lymphocyte attenuator)(BTLA)、細胞傷害性Tリンパ球関連タンパク質4(CTLA−4、CD152としても公知)、インドールアミン2,3−ジオキシゲナーゼ(IDO)、キラー細胞免疫グロブリン(KIR)、リンパ球活性化遺伝子−3(LAG3)、プログラム細胞死1(PD−1)、T細胞免疫グロブリンドメインおよびムチンドメイン3(TIM−3)、ならびにT細胞活性化のVドメインIg抑制因子(VISTA)が挙げられる。特に、上記免疫チェックポイントインヒビターは、PD−1軸および/またはCTLA−4を標的とする。
T細胞機能不全またはアネルギーは、阻害性レセプター、プログラム細胞死1ポリペプチド(PD−1)の、誘導されかつ持続された発現と同時に起こる。従って、PD−1およびPD−1との相互作用を通じてシグナル伝達する他の分子(例えば、プログラム細胞死リガンド1(PD−L1)およびプログラム細胞死リガンド2(PD−L2))の治療的標的化が、本明細書で提供される。PD−L1は、多くのがんにおいて過剰発現され、しばしば予後不良と関連する(Okazaki Tら, Intern. Immun. 2007 19(7):813)。従って、p53および/またはMDA−7遺伝子治療との併用でのPD−L1/PD−1相互作用の阻害は、例えば、腫瘍のCD8+ T細胞媒介性死滅を増強するために本明細書で提供される。
本明細書で提供される方法において標的化され得る別の免疫チェックポイントは、細胞傷害性Tリンパ球関連タンパク質4(CTLA−4)(CD152としても公知)である。ヒトCTLA−4の完全cDNA配列は、Genbankアクセッション番号L15006を有する。CTLA−4は、T細胞の表面上で見出され、抗原提示細胞の表面上のCD80またはCD86に結合した場合に、「オフ」スイッチとして作用する。CTLA4は、ヘルパーT細胞の表面上で発現されかつ阻害性シグナルをT細胞へと伝える、免疫グロブリンスーパーファミリーのメンバーである。CTLA4は、T細胞共刺激タンパク質、CD28に類似であり、その両方の分子は、抗原提示細胞上のCD80およびCD86(それぞれ、B7−1およびB7−2とも称される)に結合する。CTLA4は、阻害性シグナルをT細胞へと伝えるのに対して、CD28は、刺激シグナルを伝える。細胞内CTLA4はまた、調節性T細胞において見出され、それらの機能にとって重要であり得る。T細胞レセプターおよびCD28を通じてのT細胞活性化は、CTLA−4(B7分子の阻害性レセプター)の増大した発現をもたらす。
本発明における使用のための別の免疫チェックポイントインヒビターは、抗KIR抗体である。本発明における使用に適した抗ヒトKIR抗体(またはこれに由来するVH/VLドメイン)は、当該分野で周知の方法を使用して生成され得る。
本明細書で提供されるのは、個体においてがんを処置するかまたはがんの進行を遅らせるための方法であり、上記方法は、少なくとも1種の免疫チェックポイントインヒビター(例えば、PD−1軸結合アンタゴニストおよび/またはCTLA−4抗体)の有効量および少なくとも1種の腫瘍抑制遺伝子治療(例えば、p53および/またはMDA−7遺伝子治療)を上記個体に投与する工程を包含する。
本明細書で提供される併用療法は、免疫チェックポイントインヒビター(例えば、PD−1軸結合アンタゴニストおよび/またはCTLA−4抗体)ならびにp53および/またはMDA−7遺伝子治療の投与を含む。その併用療法は、当該分野で公知の任意の適切な様式で投与され得る。例えば、免疫チェックポイントインヒビター(例えば、PD−1軸結合アンタゴニストおよび/またはCTLA−4抗体)ならびにp53および/またはMDA−7遺伝子治療は、逐次的に(異なる時間で)または同時に(同じ時間に)投与され得る。いくつかの実施形態において、1もしくはこれより多くの免疫チェックポイントインヒビターは、p53および/またはMDA−7遺伝子治療あるいはその発現構築物として別個に組成物中にある。いくつかの実施形態において、免疫チェックポイントインヒビターは、p53および/またはMDA−7遺伝子治療と同じ組成物中にある。ある特定の局面において、被験体は、少なくとも1種の免疫チェックポイントインヒビターの前、同時、または後に、p53をコードする核酸および/またはMDA−7をコードする核酸を投与される。
ヒトp53およびMDA−7タンパク質をコードする1もしくはこれより多くの発現構築物、ならびに/または免疫チェックポイントインヒビターを、本発明において過剰増殖性細胞に送達するための1つの方法は、腫瘍内注射を介するものである。しかし、本明細書で開示される薬学的組成物は、代わりに、米国特許第5,543,158号、同第5,641,515号および同第5,399,363号(全て本明細書に参考として援用される)に記載されるように、非経口的に、静脈内に、皮内に、筋肉内に、経皮的に、またはさらに腹腔内に投与され得る。
p53および/またはMDA−7核酸、ならびに少なくとも1種の免疫チェックポイントインヒビターの有効性を増大させるために、それらは、がんの処置において有効な少なくとも1種のさらなる薬剤と併用され得る。より一般には、これらの他の組成物は、細胞を死滅させるかまたは細胞の増殖を阻害するために有効な併用量で提供される。このプロセスは、細胞と発現構築物および薬剤または複数の因子とを同時に接触させる工程を包含し得る。これは、細胞と、単一組成物もしくは両方の薬剤を含む薬理学的製剤とを接触させることによって、または細胞と2種の別個の組成物もしくは製剤とを同時に接触させる(ここで一方の組成物は、発現構築物を含み、他方の組成物は、第2の薬剤を含む)ことによって達成され得る。あるいは、発現構築物は、増殖しつつある細胞と接触させ得、さらなる治療が、抗腫瘍免疫応答および治療効力を増強するための免疫系または腫瘍微小環境の他の細胞に影響を及ぼし得る。その少なくとも1種のさらなる抗がん治療は、外科的療法、化学療法(例えば、プロテインキナーゼインヒビターまたはEGFR標的化治療の投与)、放射線療法、凍結療法、温熱療法、光線療法、ラジオ波焼灼療法、ホルモン療法、免疫療法、低分子療法、レセプターキナーゼインヒビター療法、抗血管新生療法、サイトカイン療法または生物学的療法(例えば、モノクローナル抗体、siRNA、miRNA、アンチセンスオリゴヌクレオチド、リボザイムまたは遺伝子治療)であり得るが、これらに限定されない。限定されないが、その生物学的療法は、遺伝子治療(例えば、腫瘍抑制遺伝子治療)、細胞死タンパク質遺伝子治療、細胞周期調節因子遺伝子治療、サイトカイン遺伝子治療、毒素遺伝子治療、免疫遺伝子治療、自殺遺伝子治療、プロドラッグ遺伝子治療、抗細胞増殖遺伝子治療、酵素遺伝子治療、または抗血管新生因子遺伝子治療であり得る。
A/B/A B/A/B B/B/A A/A/B A/B/B B/A/A A/B/B/B B/A/B/B
B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A
B/A/B/A B/A/A/B A/A/A/B B/A/A/A A/B/A/A A/A/B/A。
がん治療は一般に、化学的および放射線ベースの処置の両方との種々の併用療法も含み得る。併用化学療法剤としては、例えば、以下が挙げられる:シスプラチン(CDDP)、カルボプラチン、プロカルバジン、メクロレタミン、シクロホスファミド、カンプトテシン、イホスファミド、メルファラン、クロラムブシル、ブスルファン、ニトロソウレア、ダクチノマイシン、ダウノルビシン、ドキソルビシン、ブレオマイシン、プリカマイシン、マイトマイシン、エトポシド(VP16)、タモキシフェン、ラロキシフェン、エストロゲンレセプター結合剤、タキソール、ゲムシタビン(gemcitabien)、ナベルビン、ファルネシルプロテイントランスフェラーゼインヒビター(famesyl−protein transferase inhibitor)、トランス白金、5−フルオロウラシル、ビンクリスチン、ビンブラスチンおよびメトトレキサート、テモゾロミド(DTICの水性形態)、または前述のうちのいずれかのアナログもしくは派生改変体。化学療法と生物学的療法との併用は、バイオ化学療法として公知である。その化学療法はまた、メトロノミック化学療法として公知である低い連続用量で投与され得る。
DNA損傷を引き起こしかつ広範に使用されている他の因子としては、γ線(y−rays)、X線、および/または腫瘍細胞への放射性同位体の指向された送達として一般に公知のものが挙げられる。DNA損傷因子の他の形態はまた、公知である(例えば、マイクロ波およびUV照射)。これらの因子全てが、DNAに対して、DNAの前駆物質に対して、DNAの複製および修復に対して、ならびに染色体のアセンブリおよび維持に対して広い範囲の損傷をもたらす可能性は極めて高い。X線に関する線量範囲は、長期間(3〜4週間)に関しては50〜200レントゲンの1日線量から2000〜6000レントゲンの単一線量までの範囲に及ぶ。放射線同位体に関する線量範囲は、広く変動し、同位体の半減期、放射される放射線の強度およびタイプ、ならびに新生物細胞による取り込みに依存する。
免疫療法剤は、一般に、がん細胞を標的化しかつ破壊するために、免疫エフェクター細胞および分子の使用に依拠する。免疫エフェクターは、例えば、腫瘍細胞の表面上のある種のマーカーに特異的な抗体であり得る。抗体単独は、治療のエフェクターとして働き得るか、または細胞死滅を実際にもたらすために他の細胞を動員し得る。抗体はまた、薬物または毒素(化学療法剤、放射性核種、リシンA鎖、コレラ毒素、百日咳毒素など)に結合体化され得、標的化薬剤としてのみ働き得る。あるいは、エフェクターは、腫瘍細胞標的と、直接的または間接的のいずれかで相互作用する表面分子を有するリンパ球であり得る。種々のエフェクター細胞としては、細胞傷害性T細胞およびNK細胞、ならびにキメラ抗原レセプターを発現するように改変されたこれら細胞タイプの遺伝子操作された改変体が挙げられる。腫瘍細胞へのMda−7遺伝子移入は、腫瘍細胞死およびアポトーシスを引き起こす。アポトーシス腫瘍細胞は、樹状細胞およびマクロファージを含む細網内皮細胞によって取り除かれ、抗腫瘍免疫を生成するために免疫系へと提示される(Rovereら, 1999; Steinmanら, 1999)。
がんの受動免疫療法に関しては、多くの異なるアプローチが存在する。それらは、以下へと大まかに分類され得る:抗体のみの注射;毒素または化学療法剤と対にした抗体の注射;放射活性同位体と対にした抗体の注射;抗イディオタイプ抗体の注射;ならびに最後に、骨髄における腫瘍細胞のパージ。
能動免疫療法において、抗原性ペプチド、ポリペプチドもしくはタンパク質、または自己由来もしくは同種異系腫瘍細胞の組成物または「ワクチン」は、一般に、別個の細菌アジュバントとともに投与される(Ravindranath & Morton, 1991; Morton & Ravindranath, 1996; Mortonら, 1992; Mitchellら, 1990; Mitchellら, 1993)。黒色腫免疫療法において、高いIgM応答を誘起するそれらの患者はしばしば、全く誘起しないもしくは低いIgM抗体を誘起する患者より良好に生存する(Mortonら, 1992)。IgM抗体はしばしば、一過性の抗体であり、規則に対する例外は、抗ガングリオシドまたは抗炭水化物抗体であるようである。
養子免疫療法において、患者の循環リンパ球、または腫瘍浸潤リンパ球は、インビトロで単離され、リンホカイン(例えば、IL−2)によって活性化されるか、または腫瘍壊死に関する遺伝子で形質導入され、再投与される(Rosenbergら, 1988; 1989)。これを達成するために、動物、またはヒト患者に、本明細書で記載されるとおりのアジュバントを組み込んだ抗原性ペプチド組成物と併用して、活性化リンパ球の免疫学上有効な量が投与される。活性化リンパ球は、最も好ましくは、血液または腫瘍サンプルから先に単離され、そしてインビトロで活性化された(または「拡大された」)その患者自身の細胞である。免疫療法のこの形態は、黒色腫および腎臓がんの退縮のいくつかの症例を生じたが、応答者のパーセンテージは、応答しなかった者と比較して小さかった。より近年になって、このような養子免疫細胞治療が、キメラ抗原レセプター(CAR)を発現する遺伝子操作されたT細胞を組み込んだ(CAR T細胞治療といわれる)場合に、より高い応答率が観察された。同様に、ナチュラルキラー細胞が、自己由来および同種異系ともに単離され、拡大され、レセプターまたはリガンドを発現して、腫瘍細胞のそれらの結合および死滅を促進するように遺伝子改変されている。
他の薬剤が、処置の治療効力を改善するために、本明細書で提供される組成物と併用され得ることは企図される。これらのさらなる薬剤としては、免疫調節性薬剤、細胞表面レセプターおよびGAP結合のアップレギュレーションに影響を及ぼす薬剤、細胞増殖抑制剤および分化因子、細胞接着のインヒビター、またはアポトーシス誘導因子に対する過剰増殖性細胞の感受性を増大させる薬剤が挙げられる。免疫調節性薬剤としては、以下が挙げられる:腫瘍壊死因子;インターフェロンα、β、およびγ;IL−2および他のサイトカイン;F42Kおよび他のサイトカインアナログ;またはMIP−1、MIP−1β、MCP−1、RANTES、ならびに他のケモカイン。細胞表面レセプターまたはそれらのリガンド(例えば、Fas/Fasリガンド、DR4またはDR5/TRAIL)のアップレギュレーションは、過剰増殖性細胞に対する自己分泌または傍分泌効果の確立によって、本明細書で提供される組成物のアポトーシス誘導能力を強化することは、さらに企図される。GAP結合の数を上昇させることによって、細胞内シグナル伝達が増大すると、隣接する過剰増殖性細胞集団に対する抗過剰増殖効果が増大する。他の実施形態において、細胞増殖抑制剤または分化因子は、処置の抗過剰増殖性効力を改善するために、本明細書で提供される組成物と併用され得る。細胞接着のインヒビターは、本発明の効力を改善することが企図される。細胞接着インヒビターの例は、接着斑キナーゼ(focal adhesion kinase)(FAK)インヒビターおよびロバスタチンである。アポトーシスに対する過剰増殖性細胞の感受性を増大させる他の薬剤(例えば、抗体c225)が、処置効力を改善するために、本明細書で提供される組成物と併用され得ることは、さらに企図される。
少なくとも1種の免疫チェックポイントインヒビター(例えば、抗PD−1抗体および/または抗CTLA−4抗体)ならびにp53をコードする核酸および/またはMDA−7をコードする核酸(例えば、ad−p53および/またはad−MDA−7)を含む製造物品またはキットもまた、本明細書で提供される。製造物品またはキットは、少なくとも1種のチェックポイントインヒビターを腫瘍抑制遺伝子治療と併用して、個体においてがんを処置するかもしくはその進行を遅らせる、またはがんを有する個体の免疫機能を増強するための説明書を含むパッケージ挿入物をさらに含み得る。本明細書に記載される、免疫チェックポイントインヒビターならびにp53をコードする核酸および/またはMDA−7をコードする核酸のうちのいずれかは、製造物品またはキットの中に含まれ得る。キットは、細胞外マトリクス分解タンパク質または細胞外マトリクス分解タンパク質をコードする発現構築物をさらに含み得る。
以下の実施例は、本発明の好ましい実施形態を示すために含まれる。以下の実施例の中で開示される技術は、本発明の実施において十分に機能するように本発明者らによって発見された技術を表し、従って、その実施の好ましい態様を構成すると考えられ得ることは、当業者によって認識されるはずである。しかし、当業者は、本開示に鑑みて、多くの変更が開示される具体的実施形態において行われ得、本発明の趣旨および範囲から逸脱することなく同様のまたは類似の結果をなお得ることができることを認識するはずである。
動物、腫瘍接種および測定: C57BL/6(B6)マウス(6〜8週齢)を利用した。動物に、B16F10黒色腫細胞(ATCC、5×105 細胞/マウス)を右側腹部へと皮下注射して、「原発性腫瘍」を形成した。処置を、腫瘍がおよそ50mm3のサイズに達したときに開始し、これを、処置1日目と称した。腫瘍増殖を、腫瘍の長さ(L)および幅(w)を測定することによってモニターし、腫瘍容積を、以下の式を使用して計算した:容積=0.523L(w)2。動物を、60日間までモニターし、腫瘍がおよそ2000mm3に達したときに屠殺した。
腫瘍抑制因子の併用によって誘導される抗腫瘍効果を決定するために、Ad−p53およびAd−IL24を併用し、最終処置調製物中で各ベクターの元々の用量のうちの50%を使用して、上記で記載されるように投与した。動物を、原発性腫瘍容積に関して評価した。(図7)に示されるように、抗PD−1単剤療法で処置した動物において重篤な腫瘍進行が存在したのに対して、Ad−p53+Ad−IL24の併用は、低減した腫瘍増殖を示した。抗PD−1抵抗性の改善は、Ad−p53+Ad−IL24+抗PD1の併用で処置した動物において観察され、その併用は、抗PD1またはAd−p53+Ad−IL24治療いずれか単独と比較して、原発性腫瘍容積において最大の低減を誘導した。各処置に関する腫瘍容積の統計的分散分析(ANOVA)比較は、Ad−p53+Ad−IL24+抗PD−1処置の併用効果が、処置の14日目までに相乗効果的であることを決定した(p値=0.035)。さらに、腫瘍増殖の速度の評価(反復測定ANOVA統計分析を使用)はまた、単剤療法として使用されるいずれの薬剤も超える併用処置の相乗効果を確認した(p=0.01)。
動物、腫瘍接種および測定、Ad−IL24ベクター処置および抗体処置を、実施例1に記載されるように利用した。
腫瘍抑制因子免疫遺伝子治療の抗腫瘍効果が、腫瘍微小環境の変更によって増強され得るか否かを決定するために、Ad−L24処置を、細胞外マトリクスを分解するリラキシンを発現する複製可能アデノウイルスベクターと併用した。Ad−リラキシン(Ad−RLX)およびAd−IL24を併用し、最終処置調製物中で3×1010 −vpと併用したAd−RLXの2×1010 vpの併用用量を使用して、上記の実施例2に記載されるように、抗PD−1とともに投与した。動物を、原発性腫瘍容積に関して評価した。(図10)に示されるように、抗PD−1単剤療法で処置した動物において重篤な腫瘍進行が存在したのに対して、Ad−RLX+Ad−IL24の併用は、低減した腫瘍増殖を示した。抗PD−1抵抗性の改善は、Ad−RLX+Ad−IL24+抗PD1の併用で処置した動物において観察され、その併用は、抗PD1またはAd−RLX+Ad−IL24治療いずれかと比較して、原発性腫瘍容積において最大の低減を誘導した。11日目での腫瘍容積の多重比較のための統計的分散分析(ANOVA)を行って、処置効果を比較した。PBS 対 抗PD−1処置の間には統計的有意差はなかった(P=0.8343)一方で、PBS 対 Ad−RLX+Ad−IL24(P=0.0416)およびPBS 対 Ad−RLX+Ad−IL24+抗PD−1(P=0.0039)は両方ともに、PBSコントロールと比較して、腫瘍サイズにおいて統計的に有意な低減を示した。抗PD−1 対 Ad−RLX+Ad−IL24処置の間には統計的有意差がなかった(P=0.0929)一方で、抗PD−1 対 Ad−RLX+Ad−IL24+抗PD−1群の間の差は、統計的に有意であり(P=0.0049)、Ad−RLX+Ad−IL24+抗PD−1併用の優れた効力を示した。
これらの研究を、腫瘍抑制因子治療を1日目に免疫チェックポイントインヒビター処置と同時に開始したことを除いて、実施例1において上記で記載される実験と類似の様式で行った。実験における他の差異は、以下の説明の中で注記される。
腫瘍抑制因子免疫療法の局所領域効力および遠達効力は、放射線療法および化学放射線療法とのその併用によってさらに増強され得る。p53、IL24およびリラキシンウイルスベクター、化学療法、サイトカイン療法、免疫チェックポイントインヒビター処置の動物モデルおよび処置スケジュール、ならびにそれらの最も有効な併用は、実施例1〜5において上記で記載されるものと同じである。腫瘍がおよそ50mm3に達したときに、動物を処置群へと無作為化する。上記処置群は、コントロール(生理食塩水またはPBS注射)、放射線単独(6日目に、一度に5グレイ)、および放射線(6日目に、一度に5グレイ)を与えるか与えない、上記の実施例1〜5に記載される処置群を含む。各処置群は、最低でも5〜10匹の動物を含む。腫瘍サイズおよび動物の生存を測定し、データを、上記の実施例1〜5に記載されるとおりに分析する。これは、放射線との併用処置の増大した効力を示す。
この治療アプローチの別の実施形態において、新規な腫瘍溶解性単純ヘルペスウイルスベクター(rRp450と称される)をさらなる治療用ウイルスとして使用して、上記の実施例1〜6で記載されるアプローチの効力を増強する。このrRp450ベクターを、複製し、腫瘍細胞を選択的に死滅させるように操作する;その構造および改変は、(Aghiら 1999)にさらに記載される。簡潔には、そのrRp450ベクターは、ICP6(RR3活性を提供し、静止している細胞におけるウイルス複製および溶解に必須である(Chaseら, 1998)ペプチド)をコードする遺伝子が欠失した単純ヘルペスウイルスタイプ1に基づく。そのベクターはまた、シクロホスファミド(CPA)感受性ラットシトクロムp450 2B1の発現、およびガンシクロビル(GCV)感受性単純ヘルペスウイルスチミジンキナーゼ(HSV−TK)導入遺伝子の発現をコードする。
TVEC(以前は、OncoVexGM−CSF)は、欠失させたICP34.5遺伝子(腫瘍細胞ではウイルス複製を付与するが、正常な細胞では付与しない)および欠失させたICP47遺伝子(そのウイルスに対する免疫応答の抑制を生じる)の代わりにヒトGM−CSF導入遺伝子を含む複製欠損HSVベクターである。TVECは、実験株ではなく、ウイルス感染したヒトから採取された単純ヘルペスウイルス1(HSV−1)の株を遺伝子操作することによって作製された(Liuら, 2003)。
この治療アプローチの別の実施形態において、新規な腫瘍溶解性ワクシニアウイルス(VVL 15−N1L−IL12と称される)を、さらなる治療用ウイルスとして使用して、上記の実施例1〜9に記載されるアプローチの効力を増強する。数株の腫瘍溶解性ワクシニアウイルスが報告されている(例えば、Western Reserve、WyethおよびLister株)。これらの株の各々の種々の欠失変異体が作り出されている。Wangら(特許WO2015/150809A1)は、増強された選択性および抗腫瘍効力を示す不活性化N1L遺伝子を有するTK欠損ワクシニアウイルス株を開発した。N1Lは、感染した細胞のアポトーシスおよびNF−kB活性化を阻害すると考えられる。N1L遺伝子欠失は、ナチュラルキラー(NK)細胞応答を調節することに加えて、NF−kBによって制御される炎症促進性抗ウイルスサイトカインの増大をもたらすことが示された。N1L欠失誘導体は、Wangら, 2015(特許WO2015/150809A1)に記載される。VVL 15N1Lの抗腫瘍効力を増強するために、GM−CSF、IL−12、IL−21、腫瘍抑制因子および他の治療用遺伝子を、VVL 15N1LベクターのN1L領域に挿入する。これらの治療「武装した(armed)」VVL 15N1Lベクターを、処置の局所効果および遠達効果を増強するために、上記の実施例1〜8に記載されるとおりに使用する。
実施例1〜9に記載されるウイルスおよび治療の併用は、この実施例に記載されるように、治療効力をさらに増強し得る。3×106 HPD−1NRシリアン・ハムスター膵臓がん細胞を、5〜6週齢のシリアン・ハムスターの一方の側腹部に皮下移植する。腫瘍異種移植片が約8mm直径(およそ300〜350mm3)に増殖したとき、種々のウイルスおよびビヒクル緩衝液を、以下の表中に列挙した群において腫瘍内注射する。
フェーズ1安全性ステージを設計して、Ad−p53+メトロノミックカペシタビンおよび抗PD−1の最大耐量(MTD)を決定する。フェーズ1ステージの完了および至適Ad−p53用量の選択の後に、無作為コントロールフェース2治験を行う。フェーズ2治験は、フェーズ1治験において規定されたAd−p53 MTDを使用する。フェーズ2研究を、Ad−p53+カペシタビン+免疫チェックポイントインヒビター治療が、カペシタビン+免疫チェックポイントインヒビター処置単独より優れているか否かを決定するために適切かつ十分にコントロールされた治験であるように設計する。
抗PD−1処置は、進行して切除不能な疾患を有する黒色腫患者に関して承認された治療となった。抗PD−1は、多くの患者に利益をもたらす画期的処置を代表する一方で、複数の研究からの臨床データは、患者のうちの大部分が、この治療に応答しないことを示す。
・0.5cmまでの最長直径の腫瘍に関しては、0.1mLまで。
・0.5〜1.5cmの最長直径の腫瘍に関しては、0.5mLまで。
・1.5〜2.5cmの最長直径の腫瘍に関しては、1.0mLまで。
・2.5〜5cmの最長直径の腫瘍に関しては、2.0mLまで。
Claims (74)
- 被験体においてがんを処置するための方法であって、該方法は、:
(a)p53をコードする核酸および/またはMDA−7をコードする核酸の有効量を該被験体に投与する工程;ならびに
(b)少なくとも1種の免疫チェックポイントインヒビターを投与する工程
を包含する方法。 - 前記少なくとも1種のチェックポイントインヒビターは、CTLA−4、PD−1、PD−L1、PD−L2、LAG−3、BTLA、B7H3、B7H4、TIM3、KIR、またはA2aRのインヒビターから選択される、請求項1に記載の方法。
- 前記少なくとも1種の免疫チェックポイントインヒビターは、ヒトプログラム細胞死1(PD−1)軸結合アンタゴニストである、請求項1に記載の方法。
- 前記PD−1軸結合アンタゴニストは、PD−1結合アンタゴニスト、PDL1結合アンタゴニストおよびPDL2結合アンタゴニストからなる群より選択される、請求項3に記載の方法。
- 前記PD−1軸結合アンタゴニストは、PD−1結合アンタゴニストである、請求項3に記載の方法。
- 前記PD−1結合アンタゴニストは、PDL1および/またはPDL2へのPD−1の結合を阻害する、請求項4に記載の方法。
- 前記PD−1結合アンタゴニストは、モノクローナル抗体またはその抗原結合フラグメントである、請求項4に記載に方法。
- 前記PD−1結合アンタゴニストは、ニボルマブ、ペンブロリズマブ、ピディリズマブ、AMP−514、REGN2810、CT−011、BMS 936559、MPDL328OAまたはAMP−224である、請求項4に記載の方法。
- 前記少なくとも1種の免疫チェックポイントインヒビターは、抗CTLA−4抗体である、請求項1に記載の方法。
- 前記抗CTLA−4抗体は、トレメリムマブまたはイピリムマブである、請求項9に記載の方法。
- 前記少なくとも1種の免疫チェックポイントインヒビターは、抗キラー細胞免疫グロブリン様レセプター(KIR)抗体である、請求項1に記載の方法。
- 前記抗KIR抗体は、リリルマブである、請求項11に記載の方法。
- 1種より多くのチェックポイントインヒビターが投与される、請求項1に記載の方法。
- 前記免疫チェックポイントインヒビターは、全身投与される、請求項1に記載の方法。
- 細胞外マトリクス分解タンパク質を提供する工程をさらに包含する、請求項1に記載の方法。
- 提供する工程は、前記細胞外マトリクス分解タンパク質をコードする発現カセットを投与する工程を包含する、請求項15に記載の方法。
- 前記細胞外マトリクス分解タンパク質は、リラキシン、ヒアルロニダーゼまたはデコリンである、請求項15に記載の方法。
- 前記発現カセットは、ウイルスベクター中にある、請求項16に記載の方法。
- 前記ウイルスベクターは、アデノウイルスベクター、レトロウイルスベクター、ワクシニアウイルスベクター、アデノ随伴ウイルスベクター、ヘルペスウイルスベクター、水疱性口炎ウイルスベクター、またはポリオーマウイルスベクターである、請求項18に記載の方法。
- 前記細胞外マトリクス分解タンパク質は、工程(a)の前に提供される、請求項15に記載の方法。
- 前記細胞外マトリクス分解タンパク質をコードする発現カセットは、腫瘍内に、動脈内に、静脈内に、血管内に、胸腔内に、腹腔内に、気管内に、髄腔内に、筋肉内に、内視鏡的に、病変内に、経皮的に、皮下に、局部的に、立体戦略的に、または直接注射もしくは灌流によって投与される、請求項16に記載の方法。
- 前記細胞外マトリクス分解タンパク質をコードする発現カセットは、腫瘍内に投与される、請求項16に記載の方法。
- 前記がんは、黒色腫、非小細胞肺がん、小細胞肺がん、肺がん、肝細胞がん、網膜芽腫、星状細胞腫、膠芽腫、白血病、神経芽腫、頭部がん、頚部がん、乳がん、膵臓がん、前立腺がん、腎臓がん、骨がん、精巣がん、卵巣がん、中皮腫、子宮頚がん、消化管がん、泌尿生殖器がん、呼吸路のがん、造血細胞のがん、筋骨格系のがん、神経内分泌のがん、癌腫、肉腫、中枢神経系のがん、末梢神経系のがん、リンパ腫、脳のがん、結腸がんまたは膀胱がんである、請求項1に記載の方法。
- 前記がんは、転移性である、請求項1に記載の方法。
- 前記p53をコードする核酸および/または前記MDA−7をコードする核酸は、発現カセット中にある、請求項1に記載の方法。
- 発現カセットは、ウイルスベクター中にある、請求項25に記載の方法。
- 前記ウイルスベクターは、アデノウイルスベクター、レトロウイルスベクター、ワクシニアウイルスベクター、アデノ随伴ウイルスベクター、ヘルペスウイルスベクター、水疱性口炎ウイルスベクター、またはポリオーマウイルスベクターである、請求項26に記載の方法。
- 前記ウイルスベクターは、アデノウイルスベクターである、請求項26に記載の方法。
- 前記ウイルスベクターは、約103〜約1013の間のウイルス粒子で投与される、請求項26に記載の方法。
- 前記アデノウイルスベクターは、静脈内に、動脈内に、血管内に、胸腔内に、腹腔内に、気管内に、腫瘍内に、髄腔内に、筋肉内に、内視鏡的に、病変内に、経皮的に、皮下に、局部的に、立体戦略的に、または直接注射もしくは灌流によって前記被験体に投与される、請求項26に記載の方法。
- 前記アデノウイルスベクターは、腫瘍内に前記被験体へと投与される、請求項26に記載の方法。
- 前記p53をコードする核酸および/または前記MDA−7をコードする核酸、ならびに少なくとも1種の免疫チェックポイントインヒビターは、遠達効果を誘導する、請求項31に記載の方法。
- 前記被験体は、前記アデノウイルスベクターを1回より多く投与される、請求項26に記載の方法。
- 前記被験体は、前記少なくとも1種の免疫チェックポイントインヒビターの前、同時、または後に、前記p53をコードする核酸および/または前記MDA−7をコードする核酸を投与される、請求項1に記載の方法。
- 前記被験体は、前記p53をコードする核酸を投与される、請求項1に記載の方法。
- 前記被験体は、前記MDA−7をコードする核酸を投与される、請求項1に記載の方法。
- 前記被験体は、前記p53をコードする核酸および前記MDA−7をコードする核酸を投与される、請求項1に記載の方法。
- p53およびMDA−7は、単一のプロモーターの制御下にある、請求項37に記載の方法。
- 前記プロモーターは、サイトメガロウイルス(CMV)、SV40、またはPGKである、請求項38に記載の方法。
- 前記核酸は、リポプレックスにおいて前記被験体に投与される、請求項1に記載の方法。
- 前記リポプレックスは、DOTAPおよび少なくとも1種のコレステロール、コレステロール誘導体、またはコレステロール混合物を含む、請求項40に記載の方法。
- 投与する工程は、局所注射または局部注射を含む、請求項1に記載の方法。
- 投与する工程は、連続注入、腫瘍内注射、または静脈内注射を介する、請求項1に記載の方法。
- 前記被験体は、ヒトである、請求項1に記載の方法。
- 少なくとも1種のさらなる抗がん処置を投与する工程をさらに包含する、請求項1に記載の方法。
- 前記少なくとも1種のさらなる抗がん処置は、外科的療法、化学療法、放射線療法、ホルモン療法、免疫療法、低分子療法、レセプターキナーゼインヒビター療法、抗血管新生療法、サイトカイン療法、凍結療法または生物学的療法である、請求項45に記載の方法。
- 前記生物学的療法は、モノクローナル抗体、siRNA、miRNA、アンチセンスオリゴヌクレオチド、リボザイムまたは遺伝子治療である、請求項46に記載の方法。
- 前記少なくとも1種のさらなる抗がん処置は、腫瘍溶解性ウイルスである、請求項45に記載の方法。
- 前記腫瘍溶解性ウイルスは、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、ヘルペスウイルス、ポックスウイルス、ワクシニアウイルス、小胞性口炎ウイルス、ポリオウイルス、ニューカッスル病ウイルス、エプスタインバーウイルス、インフルエンザウイルスまたはレオウイルスである、請求項48に記載の方法。
- 前記腫瘍溶解性ウイルスは、単純ヘルペスウイルスである、請求項48に記載の方法。
- 前記腫瘍溶解性ウイルスは、サイトカインを発現するように操作される、請求項48に記載の方法。
- 前記サイトカインは、顆粒球マクロファージコロニー刺激因子(GM−CSF)である、請求項51に記載の方法。
- 前記腫瘍溶解性ウイルスは、talimogene laherparepvec(T−VEC)としてさらに定義される、請求項48に記載の方法。
- 前記少なくとも1種のさらなる抗がん処置は、プロテインキナーゼまたは増殖因子のシグナル伝達経路インヒビターである、請求項45に記載の方法。
- 前記プロテインキナーゼまたは増殖因子のシグナル伝達経路インヒビターは、アファチニブ、アキシチニブ、ベバシズマブ、ボスチニブ、セツキシマブ、クリゾチニブ、ダサチニブ、エルロチニブ、ホスタマチニブ、ゲフィチニブ、イマチニブ、ラパチニブ、レンバチニブ、ムブリチニブ、ニロチニブ、パニツムマブ、パゾパニブ、ペガプタニブ、ラニビズマブ、ルキソリチニブ、サラカチニブ、ソラフェニブ、スニチニブ、トラスツズマブ、バンデタニブ、AP23451、ベムラフェニブ、CAL101、PX−866、LY294002、ラパマイシン、テムシロリムス、エベロリムス、リダホロリムス、アルボシジブ、ゲニステイン、セルメチニブ、AZD−6244、バタラニブ、P1446A−05、AG−024322、ZD1839、P276−00またはGW572016である、請求項54に記載の方法。
- 前記プロテインキナーゼインヒビターは、PI3Kインヒビターである、請求項54に記載の方法。
- 前記PI3Kインヒビターは、PI3Kδインヒビターである、請求項56に記載の方法。
- 前記免疫療法は、サイトカインを含む、請求項46に記載の方法。
- 前記サイトカインは、顆粒球マクロファージコロニー刺激因子(GM−CSF)である、請求項58に記載の方法。
- 前記サイトカインは、インターロイキンおよび/またはインターフェロンである、請求項58に記載の方法。
- 前記インターロイキンは、IL−2である、請求項60に記載の方法。
- 前記インターフェロンは、IFNαである、請求項60に記載の方法。
- 前記免疫療法は、共刺激レセプターアゴニスト、先天性免疫細胞の刺激因子、または先天性免疫の活性化因子を含む、請求項46に記載の方法。
- 前記共刺激レセプターアゴニストは、抗OX40抗体、抗GITR抗体、抗CD137抗体、抗CD40抗体、または抗CD27抗体である、請求項63に記載の方法。
- 前記免疫細胞の刺激因子は、細胞傷害性阻害レセプターのインヒビターまたは免疫刺激toll様レセプター(TLR)のアゴニストである、請求項63に記載の方法。
- 前記細胞傷害性阻害レセプターは、NKG2A/CD94またはCD96 TACTILEのインヒビターである、請求項65に記載の方法。
- 前記TLRアゴニストは、TLR7アゴニスト、TLR8アゴニスト、またはTLR9アゴニストである、請求項65に記載の方法。
- 前記免疫療法は、PD−L1インヒビター、4−1BBアゴニスト、およびOX40アゴニストの組み合わせを含む、請求項46に記載の方法。
- 前記免疫療法は、インターフェロン遺伝子の刺激因子(STING)アゴニストを含む、請求項46に記載の方法。
- 前記先天性免疫の活性化因子は、IDOインヒビター、TGFβインヒビター、またはIL−10インヒビターである、請求項63に記載の方法。
- 前記化学療法は、DNA損傷因子を含む、請求項46に記載の方法。
- 前記DNA損傷因子は、γ線照射、X線、UV照射、マイクロ波、電子放出、アドリアマイシン、5−フルオロウラシル(5FU)、カペシタビン、エトポシド(VP−16)、カンプトテシン、アクチノマイシンD, マイトマイシンC、シスプラチン(CDDP)、または過酸化水素である、請求項70に記載の方法。
- 前記DNA損傷因子は、5FUまたはカペシタビンである、請求項70に記載の方法。
- 前記化学療法は、シスプラチン(CDDP)、カルボプラチン、プロカルバジン、メクロレタミン、シクロホスファミド、カンプトテシン、イホスファミド、メルファラン、クロラムブシル、ブスルファン、ニトロソウレア、ダクチノマイシン、ダウノルビシン、ドキソルビシン、ブレオマイシン、プリカマイシン、マイトマイシン、エトポシド(VP16)、タモキシフェン、タキソテール、タキソール、トランス白金、5−フルオロウラシル、ビンクリスチン、ビンブラスチン、メトトレキサート、またはこれらの任意のアナログもしくは派生改変体を含む、請求項46に記載の方法。
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Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2959563T3 (es) * | 2016-01-11 | 2024-02-27 | Univ London Queen Mary | Inhibidores de pi3k p-delta 110 para su uso en la administración de virus en el tratamiento del cáncer |
US11559510B2 (en) | 2016-04-06 | 2023-01-24 | Noxopharm Limited | Isoflavonoid composition with improved pharmacokinetics |
AU2017247006B2 (en) * | 2016-04-06 | 2022-05-12 | Noxopharm Limited | Radiotherapy improvements |
TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Hdac抑制劑與pd-l1抑制劑之組合治療 |
US20190336552A1 (en) | 2016-05-30 | 2019-11-07 | Astellas Pharma Inc. | Genetically engineered vaccinia viruses |
US10888594B2 (en) | 2016-05-30 | 2021-01-12 | National University Corporation Tottori University | Genetically engineered vaccinia viruses |
MX2019008458A (es) | 2017-01-17 | 2019-12-02 | Heparegenix Gmbh | Inhibidores de proteina cinasa para promover la regeneracion hepatica o reducir o prevenir la muerte de hepatocitos. |
CA3066054A1 (en) * | 2017-06-04 | 2018-12-13 | Rappaport Family Institute For Research In The Medical Sciences | Method of predicting personalized response to cancer therapy and kit therefor |
WO2019046619A1 (en) * | 2017-08-30 | 2019-03-07 | Sanford Burnham Prebys Medical Discovery Institute | TP53 GENE AS A BIOMARKER FOR REACTIVITY TO IMMUNOTHERAPY |
CA3079844A1 (en) * | 2017-11-10 | 2019-05-16 | Armo Biosciences, Inc. | Compositions and methods of use of interleukin-10 in combination with immune checkpoint pathway inhibitors |
US20210330696A1 (en) * | 2018-03-06 | 2021-10-28 | Rita Elena Serda | A high capacity platform for immunogenic cancer cell death |
CN112020510A (zh) * | 2018-03-19 | 2020-12-01 | 茂体外尔公司 | 包含用于治疗癌症的肿瘤抑制基因疗法和cd122/cd132激动剂的方法及组合物 |
AU2019351255A1 (en) * | 2018-09-26 | 2021-04-29 | Astellas Pharma Inc. | Cancer therapy by combination use of oncolytic vaccinia virus and immune checkpoint inhibitor, and pharmaceutical composition and combination medicine for use in the cancer therapy |
US20200113829A1 (en) * | 2018-10-12 | 2020-04-16 | Synergene Therapeutics, Inc. | Methods for reducing side effects of immunotherapy |
CN109735558B (zh) * | 2018-12-12 | 2022-04-15 | 中南大学 | 一种重组car19-il24基因、慢病毒载体、car19-il24-t细胞及应用 |
WO2020150429A1 (en) * | 2019-01-16 | 2020-07-23 | Board Of Regents, The University Of Texas System | Methods and compositions for treating immune checkpoint inhibitor associated colitis |
CN113795270A (zh) * | 2019-02-26 | 2021-12-14 | 质量基因国际公司 | 从全血移除目标对象的全血处理装置和方法 |
US20220226402A1 (en) * | 2019-03-25 | 2022-07-21 | Northshore University Health System | Methods and compositions comprising enhanced targeted immune gene therapy for the treatment of cancer |
WO2020198734A1 (en) * | 2019-03-28 | 2020-10-01 | The Penn State Research Foundation | Methods, compositions relating to treatment of cancer |
EP3970754A4 (en) * | 2019-05-14 | 2023-08-02 | Oncolys BioPharma, Inc. | METHOD FOR ADMINISTRATION OF AN ONCOLYTIC VIRUS TO TUMOR TISSUE, AND ADMINISTRATION DEVICE |
JP2022534412A (ja) * | 2019-05-30 | 2022-07-29 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | プロカスパーゼ‐3の活性化及びがんの治療のための免疫療法 |
EP3996718A1 (en) * | 2019-07-09 | 2022-05-18 | Takeda Pharmaceutical Company Limited | Administration of sting agonist and checkpoint inhibitors |
CN112646839A (zh) * | 2019-10-10 | 2021-04-13 | 梁亚龙 | 一种经修饰的腺相关病毒 |
US20230038044A1 (en) * | 2020-02-18 | 2023-02-09 | Innobation Bio Co., Ltd. | Companion diagnosis biomarker composition and companion diagnosis kit containing same |
KR102395580B1 (ko) * | 2020-02-18 | 2022-05-10 | (주)이노베이션바이오 | 동반진단용 바이오마커 조성물 및 이를 포함하는 동반진단용 키트 |
AU2021247415A1 (en) | 2020-03-30 | 2022-09-29 | Noxopharm Limited | Methods for the treatment of inflammation associated with infection |
CN111658778B (zh) * | 2020-06-11 | 2021-11-09 | 中国科学院长春应用化学研究所 | 药物组合物及其制备方法与应用 |
IL298592A (en) * | 2020-06-24 | 2023-01-01 | Pmv Pharmaceuticals Inc | Combined treatment for cancer |
MX2023003032A (es) * | 2020-09-15 | 2023-06-01 | Merck Sharp & Dohme Llc | Terapia de combinacion de un antagonista de pd-1 y un antagonista de lag3 y lenvatinib o una sal farmaceuticamente aceptable del mismo para el tratamiento de pacientes con cancer. |
CN113186225B (zh) | 2021-05-13 | 2021-11-02 | 中国医学科学院北京协和医院 | Pd1/pdl1单抗致免疫性心肌炎模型及制备方法 |
WO2023196899A2 (en) * | 2022-04-08 | 2023-10-12 | Global Cancer Technology | Methods and products to screen and treat glioblastoma multiforme and other cancers, including breast cancers, using a combination of pi3kinase inhibitors with checkpoint inhibitors |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000516618A (ja) * | 1996-08-16 | 2000-12-12 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | がん性表現型を反転させるための、メラノーマ分化関連遺伝子(mda 7)の使用 |
JP2006512097A (ja) * | 2002-12-23 | 2006-04-13 | シティ・オブ・ホープ | 癌免疫療法におけるp53を発現する改変・ワクシニア・アンカラ |
WO2015069770A1 (en) * | 2013-11-05 | 2015-05-14 | Cognate Bioservices, Inc. | Combinations of checkpoint inhibitors and therapeutics to treat cancer |
US20150250837A1 (en) * | 2012-09-20 | 2015-09-10 | Morningside Technology Ventures Ltd. | Oncolytic virus encoding pd-1 binding agents and uses of the same |
Family Cites Families (107)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5023321A (en) | 1982-12-13 | 1991-06-11 | Howard Florey Institute Of Experimental Physiology & Medicine | Molecular cloning and characterization of a further gene sequence coding for human relaxin |
US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4682195A (en) | 1985-09-30 | 1987-07-21 | General Electric Company | Insulated gate device with configured emitter contact pad |
US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
US4835251A (en) | 1986-06-23 | 1989-05-30 | Genetech, Inc. | Method of chain combination |
EP0266032A1 (en) | 1986-08-29 | 1988-05-04 | Beecham Group Plc | Modified fibrinolytic enzyme |
US5824311A (en) | 1987-11-30 | 1998-10-20 | Trustees Of The University Of Pennsylvania | Treatment of tumors with monoclonal antibodies against oncogene antigens |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5302523A (en) | 1989-06-21 | 1994-04-12 | Zeneca Limited | Transformation of plant cells |
US7705215B1 (en) | 1990-04-17 | 2010-04-27 | Dekalb Genetics Corporation | Methods and compositions for the production of stably transformed, fertile monocot plants and cells thereof |
US5550318A (en) | 1990-04-17 | 1996-08-27 | Dekalb Genetics Corporation | Methods and compositions for the production of stably transformed, fertile monocot plants and cells thereof |
US5322783A (en) | 1989-10-17 | 1994-06-21 | Pioneer Hi-Bred International, Inc. | Soybean transformation by microparticle bombardment |
US5484956A (en) | 1990-01-22 | 1996-01-16 | Dekalb Genetics Corporation | Fertile transgenic Zea mays plant comprising heterologous DNA encoding Bacillus thuringiensis endotoxin |
US5466468A (en) | 1990-04-03 | 1995-11-14 | Ciba-Geigy Corporation | Parenterally administrable liposome formulation comprising synthetic lipids |
US5384253A (en) | 1990-12-28 | 1995-01-24 | Dekalb Genetics Corporation | Genetic transformation of maize cells by electroporation of cells pretreated with pectin degrading enzymes |
US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
US6410010B1 (en) | 1992-10-13 | 2002-06-25 | Board Of Regents, The University Of Texas System | Recombinant P53 adenovirus compositions |
EP0940468A1 (en) | 1991-06-14 | 1999-09-08 | Genentech, Inc. | Humanized antibody variable domain |
US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
US5610042A (en) | 1991-10-07 | 1997-03-11 | Ciba-Geigy Corporation | Methods for stable transformation of wheat |
DE4204650C1 (ja) | 1992-02-15 | 1993-07-08 | Hoffmeister, Helmut, Dr., 4400 Muenster, De | |
EP0604662B1 (en) | 1992-07-07 | 2008-06-18 | Japan Tobacco Inc. | Method of transforming monocotyledon |
US5702932A (en) | 1992-07-20 | 1997-12-30 | University Of Florida | Microinjection methods to transform arthropods with exogenous DNA |
EP0652965A1 (en) | 1992-07-27 | 1995-05-17 | Pioneer Hi-Bred International, Inc. | An improved method of agrobacterium-mediated transformation of cultured soybean cells |
DE4228457A1 (de) | 1992-08-27 | 1994-04-28 | Beiersdorf Ag | Herstellung von heterodimerem PDGF-AB mit Hilfe eines bicistronischen Vektorsystems in Säugerzellen |
GB9222888D0 (en) | 1992-10-30 | 1992-12-16 | British Tech Group | Tomography |
US5801029A (en) | 1993-02-16 | 1998-09-01 | Onyx Pharmaceuticals, Inc. | Cytopathic viruses for therapy and prophylaxis of neoplasia |
US5801005A (en) | 1993-03-17 | 1998-09-01 | University Of Washington | Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated |
AU7326594A (en) | 1993-07-09 | 1995-02-06 | Synergen, Inc. | Recombinant ctla4 polypeptides and methods for making the same |
US5543158A (en) | 1993-07-23 | 1996-08-06 | Massachusetts Institute Of Technology | Biodegradable injectable nanoparticles |
AU695540B2 (en) | 1993-10-27 | 1998-08-13 | Trustees Of Columbia University In The City Of New York, The | Method for generating a subtracted cDNA library and uses of the generated library |
US5656610A (en) | 1994-06-21 | 1997-08-12 | University Of Southern California | Producing a protein in a mammal by injection of a DNA-sequence into the tongue |
FR2722208B1 (fr) | 1994-07-05 | 1996-10-04 | Inst Nat Sante Rech Med | Nouveau site interne d'entree des ribosomes, vecteur le contenant et utilisation therapeutique |
GB9506466D0 (en) | 1994-08-26 | 1995-05-17 | Prolifix Ltd | Cell cycle regulated repressor and dna element |
US5736524A (en) | 1994-11-14 | 1998-04-07 | Merck & Co.,. Inc. | Polynucleotide tuberculosis vaccine |
US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
IE80468B1 (en) | 1995-04-04 | 1998-07-29 | Elan Corp Plc | Controlled release biodegradable nanoparticles containing insulin |
US5811395A (en) | 1995-06-07 | 1998-09-22 | Medical University Of South Carolina | Relaxin analogs and derivatives methods and uses thereof |
US7060808B1 (en) | 1995-06-07 | 2006-06-13 | Imclone Systems Incorporated | Humanized anti-EGF receptor monoclonal antibody |
US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
US5705629A (en) | 1995-10-20 | 1998-01-06 | Hybridon, Inc. | Methods for H-phosphonate synthesis of mono- and oligonucleotides |
US5780448A (en) | 1995-11-07 | 1998-07-14 | Ottawa Civic Hospital Loeb Research | DNA-based vaccination of fish |
US5928906A (en) | 1996-05-09 | 1999-07-27 | Sequenom, Inc. | Process for direct sequencing during template amplification |
US5739169A (en) | 1996-05-31 | 1998-04-14 | Procept, Incorporated | Aromatic compounds for inhibiting immune response |
US5844905A (en) | 1996-07-09 | 1998-12-01 | International Business Machines Corporation | Extensions to distributed MAC protocols with collision avoidance using RTS/CTS exchange |
US5945100A (en) | 1996-07-31 | 1999-08-31 | Fbp Corporation | Tumor delivery vehicles |
US6413544B1 (en) | 1996-08-19 | 2002-07-02 | The United States Of America As Represented By The Department Of Health And Human Services | Liposome complexes for increased systemic delivery |
US5981274A (en) | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
US5846225A (en) | 1997-02-19 | 1998-12-08 | Cornell Research Foundation, Inc. | Gene transfer therapy delivery device and method |
US5736167A (en) | 1997-02-27 | 1998-04-07 | Chang; Hui Hwa | Mold device for making safety shoe |
AU6703198A (en) | 1997-03-21 | 1998-10-20 | Brigham And Women's Hospital | Immunotherapeutic ctla-4 binding peptides |
US5994624A (en) | 1997-10-20 | 1999-11-30 | Cotton Incorporated | In planta method for the production of transgenic plants |
US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
JP3793693B2 (ja) | 1998-12-23 | 2006-07-05 | ファイザー インコーポレーテッド | Ctla−4に対するヒトモノクローナル抗体 |
US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
WO2001053506A2 (en) | 2000-01-21 | 2001-07-26 | Biovex Limited | Virus strains for the oncolytic treatment of cancer |
WO2005003172A2 (en) | 2003-07-02 | 2005-01-13 | Innate Pharma | Pan-kir2dl nk-receptor antibodies and their use in diagnostik and therapy |
SI1648507T1 (sl) | 2003-07-24 | 2017-07-31 | Innate Pharma S.A. | Metode in sestavki za povečanje učinkovitosti terapevtskih protiteles z uporabo potenciranja spojin nk celice |
CA2557326A1 (en) * | 2004-02-24 | 2005-09-09 | Introgen Therapeutics, Inc. | Combination of ad-p53 and chemotherapy for the treatment of tumours |
US20070281041A1 (en) * | 2004-03-02 | 2007-12-06 | Introgen Therapeutics, Inc. | Compositions and Methods Involving MDA-7 for the Treatment of Cancer |
AU2005259221B2 (en) | 2004-07-01 | 2011-02-10 | Innate Pharma | Antibodies binding to receptors KIR2DL1, -2, 3 but not KIR2DS4 and their therapeutic use |
CN101103043A (zh) | 2005-01-06 | 2008-01-09 | 诺和诺德公司 | Kir结合剂和使用其的方法 |
US20090196850A1 (en) | 2005-01-06 | 2009-08-06 | Novo Nordisk A/S | Anti-Kir Combination Treatments and Methods |
EP1896582A4 (en) | 2005-05-09 | 2009-04-08 | Ono Pharmaceutical Co | HUMAN MONOCLONAL ANTIBODIES FOR PROGRAMMED DEATH 1 (MP-1) AND METHODS FOR TREATING CANCER USING ANTI-MP-1 ANTIBODIES ALONE OR ASSOCIATED WITH OTHER IMMUNOTHERAPIES |
WO2007042573A2 (en) | 2005-10-14 | 2007-04-19 | Innate Pharma | Compositions and methods for treating proliferative disorders |
CN105037549B (zh) | 2007-01-11 | 2018-09-28 | 诺和诺德公司 | 抗-kir抗体、制剂及其应用 |
EP1987839A1 (en) | 2007-04-30 | 2008-11-05 | I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
PL2170959T3 (pl) | 2007-06-18 | 2014-03-31 | Merck Sharp & Dohme | Przeciwciała przeciwko ludzkiemu receptorowi programowanej śmierci PD-1 |
EP2044949A1 (en) | 2007-10-05 | 2009-04-08 | Immutep | Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response |
RU2531758C2 (ru) | 2008-02-11 | 2014-10-27 | Куретек Лтд. | Моноклональные антитела для лечения опухолей |
EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
WO2010014784A2 (en) | 2008-08-01 | 2010-02-04 | Bristol-Myers Squibb Company | Combination of anti-ctla4 antibody with diverse therapeutic regimens for the synergistic treatment of proliferative diseases |
AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
KR20110074850A (ko) | 2008-08-25 | 2011-07-04 | 앰플리뮨, 인크. | Pd-1 길항제 및 그의 사용 방법 |
EP2367553B1 (en) | 2008-12-05 | 2017-05-03 | Novo Nordisk A/S | Combination therapy to enhance nk cell mediated cytotoxicity |
GR1006941B (el) | 2009-06-01 | 2010-08-27 | Χημικα Και Βιοφαρμακευτικα Εργαστηρια Πατρων Αε (Cbl-Patras), | Πεπτιδικη συνθεση (peptide synthesis) |
CA2769473A1 (en) | 2009-07-31 | 2011-02-03 | N.V. Organon | Fully human antibodies to btla |
AU2010286351A1 (en) | 2009-08-31 | 2012-03-15 | Amplimmune, Inc. | B7-H4 fusion proteins and methods of use thereof |
JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Pd−l1/pd−l2の同時阻害 |
US8759359B2 (en) | 2009-12-18 | 2014-06-24 | Incyte Corporation | Substituted heteroaryl fused derivatives as PI3K inhibitors |
LT2536745T (lt) | 2010-02-19 | 2016-09-26 | Xencor, Inc. | Nauji ctla4-ig imunoadhezinai |
US8802091B2 (en) | 2010-03-04 | 2014-08-12 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
US20120027727A1 (en) | 2010-07-16 | 2012-02-02 | Epeius Biotechnologies Corporation | Targeted nanoparticles for cancer and other disorders |
UA113280C2 (xx) | 2010-11-11 | 2017-01-10 | АМІНОСПИРТЗАМІЩЕНІ ПОХІДНІ 2,3-ДИГІДРОІМІДАЗО$1,2-c]ХІНАЗОЛІНУ, ПРИДАТНІ ДЛЯ ЛІКУВАННЯ ГІПЕРПРОЛІФЕРАТИВНИХ ПОРУШЕНЬ І ЗАХВОРЮВАНЬ, ПОВ'ЯЗАНИХ З АНГІОГЕНЕЗОМ | |
MX355483B (es) | 2010-11-22 | 2018-04-19 | Innate Pharma Sa | Tratamientos y métodos de modulación de célula nk para el tratamiento de malignidades hematológicas. |
EP2518071A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Imidazopyridine derivatives as PI3K inhibitors |
SG195082A1 (en) | 2011-05-25 | 2013-12-30 | Innate Pharma Sa | Anti-kir antibodies for the treatment of inflammatory disorders |
WO2013006490A2 (en) | 2011-07-01 | 2013-01-10 | Cellerant Therapeutics, Inc. | Antibodies that specifically bind to tim3 |
WO2013025779A1 (en) | 2011-08-15 | 2013-02-21 | Amplimmune, Inc. | Anti-b7-h4 antibodies and their uses |
US9422351B2 (en) | 2011-11-03 | 2016-08-23 | The Trustees Of The University Of Pennsylvania | Isolated B7-H4 specific compositions and methods of use thereof |
JP2014022858A (ja) | 2012-07-17 | 2014-02-03 | Murata Mfg Co Ltd | 電力増幅器 |
US9682143B2 (en) * | 2012-08-14 | 2017-06-20 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
EP3381942B1 (en) | 2012-08-30 | 2021-04-14 | Amgen Inc. | A method for treating melanoma using a herpes simplex virus and an immune checkpoint inhibitor |
US9388189B2 (en) | 2012-10-16 | 2016-07-12 | Almirall, S.A. | Pyrrolotriazinone derivatives as PI3K inhibitors |
EP2964241A1 (en) | 2013-03-05 | 2016-01-13 | Baylor College Of Medicine | Oncolytic virus |
WO2014164942A1 (en) | 2013-03-13 | 2014-10-09 | The Regents Of The University Of Michigan | Dual mek/pi3k inhibitors and therapeutic methods using the same |
US9308236B2 (en) | 2013-03-15 | 2016-04-12 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions |
BR112016001420A2 (pt) | 2013-08-02 | 2018-01-23 | Aduro Biotech Holdings Europe B V | combinação de agonistas de cd27 e inibição pontual imune para estimulação imune |
CA3213715A1 (en) | 2013-08-22 | 2015-02-26 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Immuno-oncolytic thereapies |
CN107011441B (zh) | 2013-09-13 | 2020-12-01 | 百济神州(广州)生物科技有限公司 | 抗pd1抗体及其作为治疗剂与诊断剂的用途 |
WO2015082376A2 (en) | 2013-12-03 | 2015-06-11 | Bayer Pharma Aktiengesellschaft | Use of pi3k-inhibitors |
GB201405834D0 (en) | 2014-04-01 | 2014-05-14 | Univ London Queen Mary | Oncolytic virus |
CN106999577B (zh) | 2014-07-16 | 2021-12-21 | 特兰斯吉恩股份有限公司 | 溶瘤病毒和免疫检查点调节因子组合 |
CN110381997A (zh) * | 2016-12-12 | 2019-10-25 | 茂体外尔公司 | 用于治疗和预防癌症和感染性疾病的包含病毒基因治疗和免疫检查点抑制剂的方法和组合物 |
-
2016
- 2016-11-07 CN CN201680075823.8A patent/CN108884159A/zh active Pending
- 2016-11-07 JP JP2018543282A patent/JP2018532810A/ja active Pending
- 2016-11-07 US US15/773,609 patent/US20190038713A1/en not_active Abandoned
- 2016-11-07 EP EP16795531.9A patent/EP3371221A2/en not_active Withdrawn
- 2016-11-07 KR KR1020187015569A patent/KR20180104597A/ko unknown
- 2016-11-07 CA CA3004530A patent/CA3004530A1/en not_active Abandoned
- 2016-11-07 WO PCT/US2016/060833 patent/WO2017079746A2/en active Application Filing
- 2016-11-07 AU AU2016349632A patent/AU2016349632A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000516618A (ja) * | 1996-08-16 | 2000-12-12 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | がん性表現型を反転させるための、メラノーマ分化関連遺伝子(mda 7)の使用 |
JP2006512097A (ja) * | 2002-12-23 | 2006-04-13 | シティ・オブ・ホープ | 癌免疫療法におけるp53を発現する改変・ワクシニア・アンカラ |
US20150250837A1 (en) * | 2012-09-20 | 2015-09-10 | Morningside Technology Ventures Ltd. | Oncolytic virus encoding pd-1 binding agents and uses of the same |
WO2015069770A1 (en) * | 2013-11-05 | 2015-05-14 | Cognate Bioservices, Inc. | Combinations of checkpoint inhibitors and therapeutics to treat cancer |
Non-Patent Citations (3)
Title |
---|
CLINICAL CANCER RESEARCH, vol. 20, no. 17, JPN6020037576, 2014, pages 4459 - 4470, ISSN: 0004581297 * |
SURGERY, vol. 136, no. 2, JPN6020037573, 2004, pages 437 - 442, ISSN: 0004581296 * |
TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY, vol. 16, no. 89, JPN6021033750, 2004, pages 171 - 185, ISSN: 0004581298 * |
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CN108884159A (zh) | 2018-11-23 |
KR20180104597A (ko) | 2018-09-21 |
WO2017079746A3 (en) | 2017-06-29 |
WO2017079746A2 (en) | 2017-05-11 |
CA3004530A1 (en) | 2017-05-11 |
AU2016349632A1 (en) | 2018-05-24 |
EP3371221A2 (en) | 2018-09-12 |
US20190038713A1 (en) | 2019-02-07 |
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