JP2021517153A - Mospd2およびt細胞またはnk細胞特異的分子に対する二重特異性抗体 電子出願された配列表の参照 - Google Patents
Mospd2およびt細胞またはnk細胞特異的分子に対する二重特異性抗体 電子出願された配列表の参照 Download PDFInfo
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- JP2021517153A JP2021517153A JP2020549031A JP2020549031A JP2021517153A JP 2021517153 A JP2021517153 A JP 2021517153A JP 2020549031 A JP2020549031 A JP 2020549031A JP 2020549031 A JP2020549031 A JP 2020549031A JP 2021517153 A JP2021517153 A JP 2021517153A
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- antigen
- mospd2
- binding fragment
- hydrochloride
- bispecific antibody
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Abstract
Description
いくつかの実施形態では、二重特異性抗体またはその抗原結合断片は、以下の抗原結合ドメインの1つ以上を含む:
ン硫酸塩、ビンカサールPFS(ビンクリスチンサルフェート)、ビンクリスチン硫酸塩、ビンクリスチン硫酸塩リポソーム、ビノレルビン酒石酸塩、VIP、ビスモデギブ、ボラクサーゼ(グルカルピダーゼ)、ボリノスタット、ヴォトリエント(パゾパニブ塩酸塩)、ウェルコボリン(ロイコボリンカルシウム)、ザーコリ(クリゾチニブ)、ゼローダ(カペシタビン)、XELIRI、XELOX、エクスジバ(デノスマブ)、ゾーフィゴ(二塩化ラジウム223)、イクスタンジ(エンザルタミド)、ヤーボイ(イピリムマブ)、ザルトラップ(Ziv‐アフリベルセプト)、ゼルボラフ(ベムラフェニブ)、ゼヴァリン(イブリツモマブチウキセタン)、ザインカード(デクスラゾキサン塩酸塩)、Ziv‐アフリベルセプト、ゾラデックス(酢酸ゴセレリン)、ゾレドロン酸、ゾリンザ(ボリノスタット)、ゾメタ(ゾレドロン酸)、ザイデリグ(イデラリシブ)、ジカディア(セリチニブ)、ザイティガ(酢酸アビラテロン)、またはそれらの組み合わせである。
一般的定義
二重特異性抗体およびその抗原結合断片
医薬組成物およびキット
使用および生産の方法
ーザ(アザシチジン)、ビンブラスチン硫酸塩、ビンカサールPFS(ビンクリスチンサルフェート)、ビンクリスチン硫酸塩、ビンクリスチン硫酸塩リポソーム、ビノレルビン酒石酸塩、VIP、ビスモデギブ、ボラクサーゼ(グルカルピダーゼ)、ボリノスタット、ヴォトリエント(パゾパニブ塩酸塩)、ウェルコボリン(ロイコボリンカルシウム)、ザーコリ(クリゾチニブ)、ゼローダ(カペシタビン)、XELIRI、XELOX、エクスジバ(デノスマブ)、ゾーフィゴ(二塩化ラジウム223)、イクスタンジ(エンザルタミド)、ヤーボイ(イピリムマブ)、ザルトラップ(Ziv‐アフリベルセプト)、ゼルボラフ(ベムラフェニブ)、ゼヴァリン(イブリツモマブチウキセタン)、ザインカード(デクスラゾキサン塩酸塩)、Ziv‐アフリベルセプト、ゾラデックス(酢酸ゴセレリン)、ゾレドロン酸、ゾリンザ(ボリノスタット)、ゾメタ(ゾレドロン酸)、ザイデリグ(イデラリシブ)、ジカディア(セリチニブ)、ザイティガ(酢酸アビラテロン)、またはそれらの組み合わせである。
実施例
材料および方法
MOSPD2サイレンシング
ウエスタンブロット法
Q−PCR
免疫組織化学染色
実施例1
MOSPD2と転移性細胞株の遊走
実施例2
MOSPD2と細胞増殖
実施例3
MOSPD2と細胞転移
実施例4
様々な種類の癌におけるMOSPD2発現
実施例5
MOSPD2遺伝子ノックダウンと癌細胞遊走
実施例6
抗MOSPD2 F(ab’)2 mAbはヒト乳癌細胞上の内因性MOSPD2に特異的に結合する
実施例7
抗MOSPD2 F(ab’)2 mAbはMDA−231癌細胞のEGF誘導性遊走を阻害する
実施例8
抗MOSPD2抗体のエピトープマッピング
実施例9
さらなる抗MOSPD2抗体
実施例10
MOSPD2の発現は、様々な種類の癌において腫瘍グレードと相関して増加する
実施例11
抗MOSPD2/抗CD3二重特異性抗体は、固形腫瘍由来の細胞を死滅させ、T細胞を活性化する
実施例12
抗MOSPD2/抗CD3二重特異性抗体は骨髄由来の癌細胞を死滅させ、T細胞を活性化する
実施例13
抗MOSPD2/抗CD3二重特異性抗体はMDA−231乳癌細胞を死滅させる
Claims (53)
- (i)MOSPD2に対する1つ以上の抗原結合ドメイン、および(ii)T細胞またはNK細胞特異的受容体分子に対する1つ以上の抗原結合ドメインを含む、二重特異性抗体またはその抗原結合断片。
- 前記T細胞またはNK細胞特異的受容体分子が、CD3、T細胞受容体(TCR)、CD28、CD16、NKG2D、Ox40、4−1BB、CD2、CD5、またはCD95である、請求項1に記載の二重特異性抗体またはその抗原結合断片。
- MOSPD2に対する前記1つ以上の抗原結合ドメインが、抗MOSPD2抗体またはその抗原結合断片のFab、Fab’、F(ab’)2、Fv、scFv、sdFv断片、重鎖可変領域、軽鎖可変領域、相補性決定領域(CDR)、重鎖CDR1、重鎖CDR2、重鎖CDR3、軽鎖CDR1、軽鎖CDR2、または軽鎖CDR3である、請求項1または2に記載の二重特異性抗体またはその抗原結合断片。
- 前記T細胞またはNK細胞特異的受容体分子がCD3であり、およびCD3に対する1つ以上の抗原結合ドメインが、抗CD3抗体またはその抗原結合断片のFab、Fab’、F(ab’)2、Fv、scFv、sdFv断片、重鎖可変領域、軽鎖可変領域、CDR、重鎖CDR1、重鎖CDR2、重鎖CDR3、軽鎖CDR1、軽鎖CDR2、または軽鎖CDR3である、請求項1〜3のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 以下の抗原結合ドメイン:
(i)抗MOSPD2抗体またはその抗原結合断片の重鎖可変領域;および
(ii)抗MOSPD2抗体またはその抗原結合断片の軽鎖可変領域
の1つ以上を含む、請求項1〜4のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。 - 以下の抗原結合ドメイン:
(i)抗CD3抗体またはその抗原結合断片の重鎖可変領域;および
(ii)抗CD3抗体またはその抗原結合断片の軽鎖可変領域
の1つ以上を含む、請求項1〜5のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。 - 以下の抗原結合ドメイン:
(i)抗MOSPD2抗体またはその抗原結合断片の重鎖可変領域;
(ii)抗MOSPD2抗体またはその抗原結合断片の軽鎖可変領域;
(iii)抗CD3抗体またはその抗原結合断片の重鎖可変領域;および
(iv)抗CD3抗体またはその抗原結合断片の軽鎖可変領域
を含む、請求項1〜6のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。 - 前記抗原結合ドメインの1つ以上がペプチドリンカーによって連結されている、請求項1〜7のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 少なくとも1つの抗原結合ドメインがヒトである、請求項1〜8のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 少なくとも1つの抗原結合ドメインがヒト化されている、請求項1〜8のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 前記二重特異性抗体またはその抗原結合断片が一本鎖ポリペプチドである、請求項1〜10のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 前記二重特異性抗体またはその抗原結合断片が、約60,000ダルトン以下の分子量を有する、請求項1〜11のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 前記二重特異性抗体が、ナノボディ、ダイアボディ、デュオボディ、CrossMab、二価抗体、二重特異性T細胞エンゲージャ(BiTE)、二重親和性再標的化(DART)、トリプルボディ、ミニ抗体、TriBiミニボディ、イントラボディ、またはクアドローマである、請求項1〜12のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 前記二重特異性抗体またはその抗原結合断片が、約10−6M〜約10−12Mの平衡解離定数(KD)でMOSPD2および/またはCD3に特異的に結合する、請求項1〜13のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 前記二重特異性抗体もしくは抗原結合断片、またはMOSPD2に対する1つ以上の抗原結合ドメインが、配列番号1〜4の1つ以上、またはその機能的変異体に特異的に結合する、請求項1〜14のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 前記二重特異性抗体もしくは抗原結合断片、またはMOSPD2に対する1つ以上の抗原結合ドメインが、配列番号5〜8の1つ以上、またはその機能的変異体によってコードされるポリペプチドに特異的に結合する、請求項1〜15のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 前記二重特異性抗体もしくは抗原結合断片、またはMOSPD2に対する1つ以上の抗原結合ドメインが、約10−6M〜約10−12MのKDでMOSPD2に特異的に結合する、請求項1〜16のいずれか一項に記載の二重特異性抗体またはその抗原結合断片。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体またはその抗原結合断片と、薬学的に許容される担体とを含む医薬組成物。
- 全身投与に適する、請求項18に記載の医薬組成物。
- 局所投与に適する、請求項18に記載の医薬組成物。
- 経口投与に適する、請求項18に記載の医薬組成物。
- 経鼻投与に適する、請求項18に記載の医薬組成物。
- 腹腔内投与に適する、請求項18に記載の医薬組成物。
- 腫瘍内投与に適する、請求項18に記載の医薬組成物。
- 静脈内投与に適する、請求項18に記載の医薬組成物。
- 筋肉内投与に適する、請求項18に記載の医薬組成物。
- 皮下投与に適する、請求項18に記載の医薬組成物。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を、癌を治療または予防するのに有効な量で対象に投与することを含む、前記対象における癌を治療または予防する方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を、癌転移を治療または予防するのに有効な量で対象に投与することを含む、前記対象における癌転移を治療または予防する方法。
- 前記対象に有効量の抗癌剤を投与することをさらに含む、請求項28または29に記載の方法。
- 前記抗癌剤が、アビラテロン酢酸エステル、アビトレキサート(メトトレキサート)、アブラキサン(パクリタキセルアルブミン安定化ナノ粒子製剤)、ABVD、ABVE、ABVE−PC、AC、AC−T、アドセトリス(ブレンツキシマブベドチン)、ADE、アドトラスツズマブエムタンシン、アドリアマイシン(塩酸ドキソルビシン)、アドルシル(フルオロウラシル)、ジマレイン酸アファチニブ、アフィニトール(エベロリムス)、アキンゼオ(ネツピタントおよびパロノセトロン塩酸塩)、アルダラ(イミキモド)、アルデスロイキン、アレムツズマブ、アリムタ(ペメトレキセド二ナトリウム)、アロキシ(パロノセトロン塩酸塩)、アンボクロリン(Ambochlorin)(クロラムブシル)、アンボクロリン(Amboclorin)(クロラムブシル)、アミノレブリン酸、アナストロゾール、アプレピタント、アレディア(パミドロン酸二ナトリウム)、アリミデックス(アナストロゾール)、アロマシン(エキセメスタン)、アラノン(ネララビン)、三酸化ヒ素、アーゼラ(オファツムマブ)、アスパラギナーゼエルウィニアクリサンテミ(Asparaginase Erwinia chrysanthemi)、アバスチン(ベバシズマブ)、アキシチニブ、アザシチジン、BEACOPP、ベセナム(カルムスチン)、ベレオダク(ベリノスタット)、ベリノスタット、ベンダムスチン塩酸塩、BEP、ベバシズマブ、ベキサロテン、ベキサール(トシツモマブおよびI 131ヨウ素トシツモマブ)、ビカルタミド、BiCNU(カルムスチン)、ブレオマイシン、ブリナツモマブ、ブリンサイト(ブリナツモマブ)、ボルテゾミブ、ボシュリフ(ボスチニブ)、ボスチニブ、ブレンツキシマブベドチン、ブスルファン、ブスルフェクス(ブスルファン)、カバジタキセル、カボザンチニブ‐S‐リンゴ酸塩、CAF、キャンパス(アレムツズマブ)、カンプトサール(イリノテカン塩酸塩)、カペシタビン、CAPOX、カルボプラチン、カルボプラチン‐タキソール、カルフィルゾミブ、カルムブリス(カルムスチン)、カルムスチン、カルムスチンインプラント、カソデックス(ビカルタミド)、CeeNU(ロムスチン)、セリチニブ、セルビジン(ダウノルビシン塩酸塩)、サーバリックス(組換えHPV二価ワクチン)、セツキシマブ、クロラムブシル、クロラムブシル−プレドニゾン、CHOP、シスプラチン、クラフェン(シクロホスファミド)、クロファラビン、CMF、コメトリク(カボザンチニブ−S−リンゴ酸塩)、COPP、COPP−ABV、コスメゲン(ダクチノマイシン)、クリゾチニブ、CVP、シクロホスファミド、サイフォス(イホスファミド)、サイラムザ(ラムシルマブ)、シタラビン、シタラビン、リポソーマル、シトサール‐U(シタラビン)、シトキサン(シクロホスファミド)、ダブラフェニブ、ダカルバジン、ダコゲン(デシタビン)、ダクチノマイシン、ダサチニブ、ダウノルビシン塩酸塩、デシタビン、デガレリクス、デニロイキンジフチトクス、デノスマブ、デポサイト(リポソーマルシタラビン)、デポフォーム(リポソーマルシタラビン)、デクスラゾキサン塩酸塩、ジヌツキシマブ、ドセタキセル、ドキシル(ドキソルビシン塩酸塩リポソーム)、ドキソルビシン塩酸塩、ドキソルビシン塩酸塩リポソーム、Dox‐SL(ドキソルビシン塩酸塩リポソーム)、DTIC−Dome(ダカルバジン)、エフデックス(フルオロウラシル)、エリテック(ラスブリカーゼ)、エレンス(エピルビシン塩酸塩)、エロキサチン(オキサリプラチン)、エルトロンボパグオラミン、イメンド(アプレピタント)、エンザルタミド、エピルビシン塩酸塩、EPOCH、アービタックス(セツキシマブ)、メシル酸エリブリン、エリベッジ(ビスモデギブ)、エルロチニブ塩酸塩、エルウィナーゼ(アスパラギナーゼエルウィニアクリサンテミ)、エトポホス(リン酸エトポシド)、エトポシド、リン酸エトポシド、エバセット(ドキソルビシン塩酸塩リポソーム)、エベロリムス、エビスタ(ラロキシフェン塩酸塩)、エキセメスタン、フェアストン(トレミフェン)、ファリーダック(パノビノスタット)、ファスロデックス(フルベストラント)、FEC、フェマラ(レトロゾール)、フィルグラスチム、フルダラ(リン酸フルダラビン)、リン酸フルダラビン、フルオロプレックス(フルオロウラシル)、フルオロウラシル、フォレックス(メトトレキサート)、フォレックスPFS(メトトレキサート)、フォルフィリ、フォルフィリ‐ベバシズマブ、フォルフィリ−セツキシマブ、フォルフィリノックス、フォルフロックス、フォロチン(プララトレキサート)、FU‐LV、フルベストラント、ガーダシル(組換えHPV四価ワクチン)、ガーダシル9(組換えHPV九価ワクチン)、ガジバ(オビヌツズマブ)、ゲフィチニブ、ゲムシタビン塩酸塩、ゲムシタビン−シスプラチン、ゲムシタビン−オキサリプラチン、ゲムツズマブオゾガマイシン、ジェムザール(ゲムシタビン塩酸塩)、ジオトリフ(ジマレイン酸アファチニブ)、グリベック(イマチニブメシル酸塩)、ギリアデル(カルムスチンインプラント)、ギリアデルウエハー(カルムスチンインプラント)、グルカルピダーゼ、酢酸ゴセレリン、ハラベン(メシル酸エリブリン)、ハーセプチン(トラスツズマブ)、組換えHPV二価ワクチン、組換えHPV九価ワクチン、組換えHPV四価ワクチン、ハイカムチン(塩酸トポテカン)、Hyper‐CVAD、イブランス(パルボシクリブ)、イブリツモマブチウキセタン、イブルチニブ、ICE、アイクルシグ(ポナチニブ塩酸塩)、イダマイシン(イダルビシン塩酸塩)、イダルビシン塩酸塩、イデラリシブ、イフェックス(イホスファミド)、イホスファミド、イホスファミダム(イホスファミド)、メシル酸イマチニブ、イムブルビカ(イブルチニブ)、イミキモド、インライタ(アキシチニブ)、イントロンA(組換えインターフェロンα−2b)、ヨウ素131トシツモマブおよびトシツモマブ、イピリムマブ、イレッサ(ゲフィチニブ)、イリノテカン塩酸塩、イストダックス(ロミデプシン)、イクサベピロン、イグゼンプラ(イクサベピロン)、ジャカフィ(リン酸ルキソリチニブ)、ジェブタナ(カバジタキセル)、カドサイラ(アドトラスツズマブエムタンシン)、ケオキシフェン(ラロキシフェン塩酸塩)、ケピバンス(パリフェルミン)、キイトルーダ(ペムブロリズマブ)、カイプロリス(カルフィルゾミブ)、酢酸ランレオチド、二トシル酸ラパチニブ、レナリドマイド、メシル酸レンバチニブ、レンビマ(メシル酸レンバチニブ)、レトロゾール、ロイコボリンカルシウム、ロイケラン(クロラムブシル)、酢酸ロイプロリド、レブラン(アミノレブリン酸)、リンフォリジン(クロラムブシル)、リポドックス(ドキソルビシン塩酸塩リポソーム)、リポソーマルシタラビン、ロムスチン、ルプロン(酢酸ロイプロリド)、ルプロンデポ(酢酸ロイプロリド)、ルプロンデポ−Ped(酢酸ロイプロリド)、ルプロンデポ3ヶ月製剤(酢酸ロイプロリド)、ルプロンデポ4ヶ月製剤(酢酸ロイプロリド)、リムパーザ(オラパリブ)、マルキボ(ビンクリスチン硫酸塩リポソーム)、マチュレーン(プロカルバジン塩酸塩)、メクロレタミン塩酸塩、メゲース(酢酸メゲストロール)、酢酸メゲストロール、メキニスト(トラメチニブ)、メルカプトプリン、メスナ、メスネックス(メスナ)、メタゾラストン(テモゾロミド)、メトトレキサート、メトトレキサートLPF(メトトレキサート)、メキサート(メトトレキサート)、メキサート‐AQ(メトトレキサート)、マイトマイシンC、ミトキサントロン塩酸塩、ミトザイトレックス(マイトマイシンC)、MOPP、モゾビル(プレリキサフォル)、ムスタルゲン(メクロレタミン塩酸塩)、ムタマイシン(マイトマイシンC)、ミレラン(ブスルファン)、マイロサール(アザシチジン)、マイロターグ(ゲムツズマブオゾガマイシン)、ナノ粒子パクリタキセル(パクリタキセル・アルブミン安定化ナノ粒子製剤)、ナベルビン(ビノレルビン酒石酸塩)、ネララビン、ネオサール(シクロホスファミド)、ネツピタントおよびパロノセトロン塩酸塩、ニューポジェン(フィルグラスチム)、ネクサバール(ソラフェニブトシル酸塩)、ニロチニブ、ニボルマブ、ノルバデックス(タモキシフェンクエン酸塩)、Nプレート(ロミプロスチム)、オビヌツズマブ、OEPA、オファツムマブ、OFF、オラパリブ、オマセタキシンメペサクシネート、オンキャスパー(ペグアスパルガーゼ)、オンタック(デニロイキンジフチトクス)、オプジーボ(ニボルマブ)、OPPA、オキサリプラチン、パクリタキセル、パクリタキセル・アルブミン安定化ナノ粒子製剤、PAD、パルボシクリブ、パリフェルミン、パロノセトロン塩酸塩、パミドロン酸二ナトリウム、パニツムマブ、パノビノスタット、パラプラット(カルボプラチン)、パラプラチン(カルボプラチン)、パゾパニブ塩酸塩、ペグアスパルガーゼ、ペグインターフェロンα‐2b、PEG‐イントロン(ペグインターフェロンα‐2b)、ペムブロリズマブ、ペメトレキセド二ナトリウム、パージェタ(ペルツズマブ)、ペルツズマブ、プラチノール(シスプラチン)、プラチノール‐AQ(シスプラチン)、プレリキサフォル、ポマリドミド、ポマリスト(ポマリドミド)、ポナチニブ塩酸塩、プララトレキサート、プレドニゾン、プロカルバジン塩酸塩、プロロイキン(アルデスロイキン)、プロリア(デノスマブ)、プロマクタ(エルトロンボパグオラミン)、プロベンジ(シプロイセルT)、プリネトール(メルカプトプリン)、プリキサン(メルカプトプリン)、二塩化ラジウム223、ラロキシフェン塩酸塩、ラムシルマブ、ラスブリカーゼ、R‐CHOP、R‐CVP、組換えヒトパピローマウイルス(HPV)二価ワクチン、組換えヒトパピローマウイルス(HPV)九価ワクチン、組換えヒトパピローマウイルス(HPV)四価ワクチン、組換えインターフェロンα‐2b、レゴラフェニブ、R‐EPOCH、レブリミド(レナリドミド)、リウマトレックス(メトトレキサート)、リツキサン(リツキシマブ)、リツキシマブ、ロミデプシン、ロミプロスチム、ルビドマイシン(ダウノルビシン塩酸塩)、ルキソリチニブリン酸塩、スクレロゾール胸膜内エアロゾル(タルク)、シルツキシマブ、シプロイセルT、ソマチュリンデポ(ランレオチド酢酸塩)、ソラフェニブトシル酸塩、スプリセル(ダサチニブ)、スタンフォードV、滅菌タルク粉末(タルク)、ステリタルク(タルク)、スチバーガ(レゴラフェニブ)、スニチニブリンゴ酸塩、スーテント(スニチニブリンゴ酸塩)、シラトロン(ペグインターフェロンα‐2b)、シルバント(シルツキシマブ)、シノビール(サリドマイド)、シンリボ(オマセタキシンメペサクシネート)、TAC、タフィンラー(ダブラフェニブ)、タルク、タモキシフェンクエン酸塩、タラビンPFS(シタラビン)、タルセバ(エルロチニブ塩酸塩)、タルグレチン(ベキサロテン)、タシグナ(ニロチニブ)、タキソール(パクリタキセル)、タキソテール(ドセタキセル)、テモダール(テモゾロミド)、テモゾロミド、テムシロリムス、サリドマイド、サロミド(サリドマイド)、チオテパ、トポサール(エトポシド)、トポテカン塩酸塩、トレミフェン、トーリセル(テムシロリムス)、トシツモマブおよびI131ヨウ素トシツモマブ、トテクト(デクスラゾキサン塩酸塩)、TPF、トラメチニブ、トラスツズマブ、トレアンダ(ベンダムスチン塩酸塩)、トリセノックス(三酸化ヒ素)、タイケルブ(二トシル酸ラパチニブ)、ユニツキシン(ジヌツキシマブ)、バンデタニブ、VAMP、ベクチビックス(パニツムマブ)、VeIP、ベルバン(ビンブラスチン硫酸塩)、ベルケイド(ボルテゾミブ)、ベルサール(ビンブラスチン硫酸塩)、ベムラフェニブ、ベペシド(エトポシド)、ビアデュール(酢酸ロイプロリド)、ビダーザ(アザシチジン)、ビンブラスチン硫酸塩、ビンカサールPFS(ビンクリスチンサルフェート)、ビンクリスチン硫酸塩、ビンクリスチン硫酸
塩リポソーム、ビノレルビン酒石酸塩、VIP、ビスモデギブ、ボラクサーゼ(グルカルピダーゼ)、ボリノスタット、ヴォトリエント(パゾパニブ塩酸塩)、ウェルコボリン(ロイコボリンカルシウム)、ザーコリ(クリゾチニブ)、ゼローダ(カペシタビン)、XELIRI、XELOX、エクスジバ(デノスマブ)、ゾーフィゴ(二塩化ラジウム223)、イクスタンジ(エンザルタミド)、ヤーボイ(イピリムマブ)、ザルトラップ(Ziv‐アフリベルセプト)、ゼルボラフ(ベムラフェニブ)、ゼヴァリン(イブリツモマブチウキセタン)、ザインカード(デクスラゾキサン塩酸塩)、Ziv‐アフリベルセプト、ゾラデックス(酢酸ゴセレリン)、ゾレドロン酸、ゾリンザ(ボリノスタット)、ゾメタ(ゾレドロン酸)、ザイデリグ(イデラリシブ)、ジカディア(セリチニブ)、またはザイティガ(酢酸アビラテロン)である、請求項30に記載の方法。 - 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を対象に投与することを含む、前記対象において腫瘍細胞を阻害または低減する方法。
- 前記腫瘍細胞の数が、対照値または参照値と比較して、少なくとも約10%、少なくとも約20%、少なくとも約30%、少なくとも約40%、少なくとも約50%、少なくとも約60%、少なくとも約70%、少なくとも約80%、少なくとも約90%、または少なくとも約100%減少する、請求項32に記載の方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を対象に投与することを含む、前記対象においてCD3を発現する細胞によるサイトカインの産生を増加させる方法。
- T細胞を、請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物と接触させることを含む、前記T細胞におけるIL−2、CD69、および/またはIFN−γの産生または濃度を増加させる方法。
- IFN−γ産生が、対照値または参照値と比較して、少なくとも約100%、少なくとも約200%、少なくとも約300%、少なくとも約400%、少なくとも約500%、少なくとも約600%、少なくとも約700%、少なくとも約800%、少なくとも約900%、または少なくとも約1000%増加する、請求項35に記載の方法。
- IFN−γ濃度が、対照値または参照値と比較して、少なくとも約1000pg/ml、少なくとも約2000pg/ml、少なくとも約3000pg/ml、少なくとも約4000pg/ml、少なくとも約5000pg/ml、少なくとも約6000pg/ml、少なくとも約7000pg/ml、少なくとも約8000pg/ml、少なくとも約9000pg/ml、または少なくとも約10000pg/ml増加する、請求項35に記載の方法。
- CD69産生が、対照値または参照値と比較して、少なくとも約1%、少なくとも約2%、少なくとも約3%、少なくとも約4%、少なくとも約5%、少なくとも約6%、少なくとも約7%、少なくとも約8%、少なくとも約9%、少なくとも約10%、少なくとも約15%、少なくとも約20%、少なくとも約25%、または少なくとも約30%増加する、請求項35に記載の方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を対象に投与することを含む、前記対象における免疫応答を刺激する方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を対象に投与することを含む、前記対象における癌細胞に対するT細胞媒介性細胞傷害性免疫応答を刺激する方法。
- T細胞を、請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物と接触させることを含む、T細胞増殖を増加させる方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項の医薬組成物を対象に投与することを含む、前記対象の腫瘍における制御性T細胞の数を減少または枯渇させる方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体またはその抗原結合断片を使用して、対象の試料中のMOSPD2の発現レベルを決定することを含む、前記対象における癌または癌転移の予測、診断、または予後判定のための方法。
- (i)請求項1〜17のいずれか一項に記載の二重特異性抗体またはその抗原結合断片を使用して、対象の試料中のMOSPD2の発現レベルを決定または定量化すること、および(ii)工程(i)で得られた前記発現レベルを対照値または参照値と比較することを含み、ここで、前記対照値または参照値に対するMOSPD2の発現レベルの増加が、癌、癌を発症する高いリスク、または癌の予後不良を示す、請求項43に記載の方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体またはその抗原結合断片を使用して、対象の試料中のMOSPD2の発現レベルを決定することを含む、前記対象における腫瘍進行または腫瘍浸潤性の予測、診断、または予後判定のための方法。
- (i)請求項1〜17のいずれか一項に記載の二重特異性抗体またはその抗原結合断片を使用して、対象の試料中のMOSPD2の発現レベルを決定または定量化すること、および(ii)工程(i)で得られた前記発現レベルを対照値または参照値と比較することを含み、ここで、前記対照値または参照値に対するMOSPD2の発現レベルの増加が、腫瘍進行または腫瘍浸潤性の予後不良を示す、請求項45に記載の方法。
- 以下の工程:
前記試料中のMOSPD2の発現レベルを定量化するように実験室に指示すること;
実験室から前記試料中のMOSPD2の発現レベルの報告を得ること;および/または
治療有効量のMOSPD2の阻害剤を前記対象に投与すること
の1つ以上をさらに含む、請求項43〜46のいずれか一項に記載の方法。 - 前記試料が、前記対象からの組織生検、腫瘍生検、または血液試料である、請求項43〜47のいずれか一項に記載の方法。
- 前記対照値または参照値が、正常組織または正常隣接組織(NAT)におけるMOSPD2の発現レベルである、請求項43〜48のいずれか一項に記載の方法。
- 前記対照値または参照値が、検出可能なMOSPD2発現がないか、または有意なMOSPD2発現がないことである、請求項43〜48のいずれか一項に記載の方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を、MOSPD2発現腫瘍を治療または予防するのに有効な量で対象に投与することを含む、前記対象におけるMOSPD2発現腫瘍を治療または予防する方法。
- 請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物を、MOSPD2発現腫瘍関連マクロファージを有する腫瘍を治療または予防するのに有効な量で対象に投与することを含む、前記対象におけるMOSPD2発現腫瘍関連マクロファージを有する腫瘍を治療または予防する方法。
- (i)請求項1〜17のいずれか一項に記載の二重特異性抗体もしくはその抗原結合断片または請求項18〜27のいずれか一項に記載の医薬組成物、および(ii)使用説明書を含むキット。
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