JP2020521780A - 癌関連免疫抑制阻害剤 - Google Patents
癌関連免疫抑制阻害剤 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Abstract
Description
本発明に従うと、表現「を含む(comprising)」、例えば「の工程を含む(comprising the steps of)」はまた、「からなる(consisting of)」、例えば「の工程からなる(consisting of the steps of)」、として理解される。
語「糖鎖改変されたFcフラグメントを有する化合物」、「糖鎖改変されたFcフラグメントを有する分子」、「糖鎖改変されたFcフラグメントを含有する化合物」、及び「糖鎖改変されたFcフラグメントを含有する分子」は、変化したグリコシル化を有する抗体のFcフラグメントを含み、変化していないグリコシル化を有する同一のFcフラグメントと比較して、Fc受容体に対してより高い親和性を上記Fcフラグメントに提供する化合物を意味する為に、本明細書において交換可能に使用されうる。
Fcフラグメント担持化合物の例示的実施態様は、本明細書に記載されている配列番号70の2本のアミノ酸鎖を含む、糖鎖改変されたFcフラグメントを含む化合物を包含する。
従って、糖鎖改変されたFcフラグメントを有する化合物の実施態様は、抗体、特に腫瘍関連抗原に対して向けられた糖鎖改変抗体、からなる。
PCT出願番号であるPCT/FR2011/050745号(国際公開番号である国際公開第/2011/141653号)、及び米国特許第9,012,607号明細書(それらのそれぞれは、参照によって本明細書内に取り込まれる)は、マウス12G4抗体に由来する新規のヒト化抗体について開示する。このヒト化抗体は、本発明の目的に照らし、AMHRII結合性剤として使用されうる。PCT出願である国際公開第/2011/141653号で開示されている特別な実施態様において、抗体は、3C23及び3C23Kとして識別される抗体である。これらの抗体の核酸配列及びポリペプチド配列は、本明細書において、配列番号1〜16として提供される。本発明の幾つかの観点において、関心のある抗AMHRII抗体は、「配列番号〜を含む軽鎖及び配列番号〜を含む重鎖を含む」と呼ばれうる。従って、様々な実施態様において、特に好ましい抗体は下記を含む:
a)配列番号2を含む軽鎖及び配列番号4を含む重鎖(リーダーを有さない3C23 VL配列及びVH配列);
b)配列番号6を含む軽鎖及び配列番号8を含む重鎖(リーダーを有さない3C23K VL配列及びVH配列);
c)配列番号10を含む軽鎖及び配列番号12を含む重鎖(リーダーを有さない3C23 軽鎖及び重鎖);
d)配列番号14を含む軽鎖及び配列番号16を含む重鎖(リーダーを有さない3C23K 軽鎖及び重鎖)。
CDRL−1:RASX1X2VX3X4X5A(配列番号71)、ここで、X1及びX2は独立して、S又はPであり、X3はR又はW又はGであり、X4はT又はDであり、及びX5はI又はTであり;
CDRL−2は、PTSSLX6S(配列番号72)であり、ここで、X6はK又はEであり;並びに
CDRL−3は、LQWSSYPWT(配列番号73)であり;
CDRH−1は、KASGYX7FTX8X9HIH(配列番号74)であり、ここで、X7はS又はTであり、X8はS又はGであり、及びX9はY又はNであり、
CDRH−2は、WIYPX10DDSTKYSQKFQG(配列番号75)であり、ここで、X10はG又はEであり、並びに
CDRH−3は、GDRFAY(配列番号76)。
VHアミノ酸配列について配列番号17
VLアミノ酸配列について配列番号34
によって定義される。
糖鎖改変された抗HER3抗体の例示的実施態様は、本明細書において9F7F11及びH4B121と呼ばれるものである。
抗HER4抗体の例示的実施態様は、本明細書においてHE4B33と呼ばれる抗体である。
本明細書で定義される、糖鎖改変されたFcフラグメントを有する化合物は、癌患者の免疫抑制状態を減少すること又はブロックすることを可能にするので、外科的処置、放射線療法処置、及び化学療法処置を含む、既知の抗癌処置の抗癌活性を強化するのに有用である。
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Sinai School of Medicine、すなわちMF−569)、ナルコシン(NSC−5366としても知られている)、ナスカピン、D−24851(Asta Medica社)、A−105972(Abbott社)、ヘミアステルリン、3−BAABU(Cytoskeleton/Mt.Sinai School of Medicine、すなわちMF−191)、TMPN(アリゾナ州立大学)、バナドセンアセチルアセトネート、T−138026(Tularik社)、モンサトロール、イナノシン(lnanocine)(すなわち、NSC−698666)、3−IAABE(Cytoskeleton/Mt. Sinai School of Medicine)、A−204197(Abbott社)、T−607(Tuiarik社、すなわちT−900607)、RPR−115781(Aventis社)、エリュテロビン(例えばデスメチルエリュテロビン、デスアエチルエルュテロビン、イソエリュテロビンA、及びZ−エリュテロビン)、カリバエオシド、カリバエオリン、ハリコンドリンB、D−64131(Asta Medica社)、D−68144(Asta Medica社)、ジアゾナミドA、A−293620(Abbott社)、NPI−2350(Nereus社)、タッカロノリドA、TUB−245(Aventis社)、A−259754(Abbott社)、ジオゾスタチン、(−)−フェニルアヒスチン(すなわち、NSCL−96F037)、D−68838(Asta Medica社)、D−68836(Asta Medica社)、ミオセベリンB、D−43411(Zentaris社、すなわちD−81862)、A−289099(Abbott社)、A−318315(Abbott社)、HTI−286(すなわちSPA−110、トリフルオロ酢酸塩)(Wyeth社)、D−82317(Zentaris社)、D−82318(Zentaris社)、SC−12983(NCI)、リン酸レスベラスタチンナトリウム、BPR−OY−007(National Health Research Institutes)、及びSSR−250411(Sanofi社)、ステロイド(例えば、デキサメタゾン)、フィナステリド、アロマターゼ阻害剤、性腺刺激ホルモン放出ホルモンアゴニスト(GnRH)(例えばゴセレリン又はロイプロリド)、副腎皮質ステロイド(例えば、プレドニゾン)、プロゲスチン(例えば、カプロン酸ヒドロキシプロゲステロン、酢酸メゲストロール、酢酸メドロキシプロゲステロン)、エストロゲン(例えばジエチルスチルベストロール(diethlystilbestrol)、エチニルエストラジオール)、抗エストロゲン薬(例えばタモキシフェン)、アンドロゲン(例えばプロピオン酸
テストステロン、フルオキシメステロン)、抗アンドロゲン物質(例えばフルタミド)、免疫刺激薬(例えばカルメット・ゲラン桿菌(Bacillus Calmette-Guerin)(BCG)、レバミソール、インターロイキン−2、α−インターフェロン等)、トリプトリド、ホモハリントニン、ダクチノマイシン、ドキソルビシン、エピルビシン、トポテカン、イトラコナゾール、ビンデシン、セリバスタチン、ビンクリスチン、デオキシアデノシン、セルトラリン、ピタバスタチン、イリノテカン、クロファジミン、5−ノニルオキシトリプタミン、ベムラフェニブ、ダブラフェニブ、エルロチニブ、ゲフィチニブ、EGFR阻害剤、上皮増殖因子受容体(EGFR)−標的療法又は治療薬(例えば、ゲフィチニブ(Iressa(商標))、エルロチニブ(Tarceva(商標))、セツキシマブ(Erbitux(商標))、ラパチニブ(Tykerb(商標))、パニツムマブ(Vectibix(商標)))、バンデタニブ(Caprelsa(商標))、アファチニブ/BIBW2992、CI−1033/カネルチニブ、ネラチニブ/HKI−272、CP−724714、TAK−285、AST−1306、ARRY334543、ARRY−380、AG−1478、ダコミチニブ/PF299804、OSI−420/デスメチルエルロチニブ、AZD8931、AEE788、ペリチニブ/EKB−569、CUDC−101、WZ8040、WZ4002、WZ3146、AG−490、XL647、PD153035、BMS−599626)、ソラフェニブ、イマチニブ、スニチニブ、ダサチニブ、ホルモン療法等を含むが、但しこれらに限定されない。抗癌剤の投与経路、用量、及び治療レジメンの詳細は、例えば、「Cancer Clinical Pharmacology」 (2005年) ed. By Jan H. M. Schellens, Howard L. McLeod and David R. Newell, Oxford University Pressに記載されているように、当技術分野において知られている。
本明細書において別途すでに記載されているように、本明細書で定義される、糖鎖改変されたFcフラグメントを有する化合物は、1以上の更なる抗癌療法との組み合わせ処置の過程、特に1以上の抑制性免疫チェックポイントタンパク質阻害剤との組み合わせ処置の過程、を含む、1以上の更なる抗癌剤との組み合わせ処置の過程において有利に使用されうる。
A.材料及び方法
キメラ12G4、ヒト化12G4及び3C23Kのクローニング
本発明のキメラ12G4(ch12G4)に従う医薬組成物が、これまでの記載に従い(27)、構築され、そして発現された。簡単に説明すると、VL及びVHDNA配列が、プロモーター、Kozak配列、及びヒトκ/IgG1定常領域の配列を含む多シストロン性のCHK622−08ベクター中に連続してサブクローニンングされた。
これまで記載されたように、異なる分子が安定的に発現された(Siberil等,2006年,Clin Immunol Orlando Fla,Vol.118:170-179)。CHO−S、HEK293、又はYB2/0細胞が、適切な線形化発現ベクターを用いて安定的にトランスフェクトされた。Ch12G4、h12G4、及び3C23K抗体がEMS(Invitrogen社)、5%の超低(Ultra-low)IgGウシ胎仔血清(FCS:fetal calf serum)(PAA社)、及び0.5g/lのG418を使用して、5〜7日間、YB2/0細胞中で産生された。3C23K−CHO−Sが、ProCHO4(Lonza社)、4mMのグルタミン、及び1g/lのG418を使用して、7日間、CHO−S細胞中で産生された。
SPR分析が、HBS−EP(GE Healthcare社)で、25℃、Bia3000又はT200装置上で実施された。親和性測定について、MISRIIが、製造業者の指示(GE Healthcare社)に従い、EDC/NHS活性化を使用して、CM5センサーチップ上に共有結合により固定化された(1000RU)。種々の濃度(0.5〜128nM)の12G4又は3C23Kが、固定化された受容体上に180秒間注入された。泳動バッファー中で400秒間解離させた後、センサーチップは、Gly−HCl(pH1.7)を使用して再生された。KD値が、親和性及びアビディティーを考慮しながら、ラングミュアの1:1フィッティングモデル(BiaEvaluation3.2、GE Healthcare社)を使用して計算された。抗体−FcγR測定が、4000〜5000RUレベルで共有結合により固定化された抗His(R&D Systems社)上で捕捉されたFcγR(Sigma社)において、単一サイクル滴定により100μl/分で実施された。γ受容体が20nMで60秒間注入され、そして5つの漸増する濃度の抗体が注入された(注入時間=60秒)。泳動バッファー中での600秒の解離工程後、センサー表面が5μlのグリシン−HCl(pH1.7)を使用して再生された。動力学的パラメーターが、T200評価ソフトウェア3.0(GE Healthcare社)上の不均質なリガンドモデル又は定常状態フィッティングモデルを使用して、センサーグラムから評価された。全てのセンサーグラムは、フィッティング評価の前に、対照参照表面(固定化されたタンパク質を一切含まない)及びバッファーブランク注入からの低シグナルを引き算することによって修正された。
マウス抗MISRII MAb 12G4が、Salhi等及びKersual等によって記載された(17,22)。抗イディオタイプ第VIII因子キメラIgG1 R565 EMABling(登録商標)MAb及び抗CEA MAb35A7(17)が無関係の抗体として使用された。
キメラ化、ヒト化、及び親和性成熟
3C23Kヒト化抗体は、マウス12G4 MAbの可変領域にそもそも由来した(Sahli等,2004年,Biochem J,Vol.37:785-793)。ヒト化手順は、CDRグラフティング(MAb h12G4)、及びランダム突然変異誘発による親和性成熟、及びファージディスプレーを含み、最終分子3C23Kをもたらした。
YB2/0細胞(EMABling(登録商標)バージョン;3C23K)(27)、CHO−S細胞(3C23K−CHO)、又はHEK293(3C23K−HEK293)細胞(機能的アッセイ用のコンパレータとして使用された)内で発現された3C23Kのオリゴ糖分析は、2つの明確に異なるグリコシル化パターンを示した。フコシル化、ガラクトシル化、及び二分化GlcNAcアイソフォームのパーセンテージ(%)は、3C23Kについてそれぞれ33.0%、57.2%、及び1.8%、並びに3C23K−CHOについてそれぞれ94.6%、54.4%、及び2.0%であった。これらグリコシル化の差異がFcγRsへの結合に対する効果が、SPRにより分析された。hFcγRIIIa及びhFcγRIIIbに対する結合親和性は、フコースが低下した後、明確に高まった(3C23K−HEK293について31〜164nM及び378nMと比較して、それぞれ、3C23Kについて1〜12nM及び86.0nM)が、しかし他のFcγR(hFcγRI、hFcγRIIa、hFcγRIIb)については当てはまらなかった(下記の実施例2の表2をまた参照)。
背景:
GM102は、クローン18H2を使用して、YB2/0細胞(ラットハイブリドーマYB2/3HL)内で産生されるヒト化モノクロナール抗体である。
a)GM102についてのグリカン分析結果:表2
PNGase FによるN−脱グリコシル化、そして放出された炭水化物残基のタグ化後に、UPLC−HILIC−FDによって、これらの炭水化物残基の分析が、6つの主要な炭水化物部分の存在を明らかにした:
1.非フコシル化(G0) 51.1%
2.フコシル化(G0F) 12.8%
3.モノガラクトシル化非フコシル化(G1) 10.2%
4.モノガラクトシル化フコシル化(G1F) 4.3 %
5.アグリコシル化非フコシル化(G0B) 9.9%
6.二分化GlcNAcを有するフコシル化(G0FB) 3.4%
フコシル化された残基の合計は、23%であった。
A.材料及び方法
表面プラズモン共鳴(SPR:Surface Plasmon Resonance)分析:
抗ヒスチジン抗体(R&D Systems社)が、製造業者の指示(GE Healthcare社)に従って、EDC/NHS活性化を使用して、CM5センサーチップ上で、10μl/分の流速、HBS−EP中、25℃でT200装置上に固定された。該抗体は、フローセルFc2上に、6900RUレベルにおいて共有結合的に固定化され、そして対照参照表面(フローセルFc1)が、同一の化学処置を使用して、しかし抗His抗体無しに調製された。
ハイポフコシル化抗AMHRII3C23K抗体のヒトFc受容体の親和性定数(Kd)の測定の結果が、下記の表4に示されている。
*KDは、異種リガンドフィッティングモデルを使用して計算された。
**フィッティングが異種リガンドモデルに当てはまらなかった場合には、KD値は、2ステート反応モデルを用いて決定された。
A.材料及び方法
イン・ビトロ(in vitro)免疫学アッセイ:
T細胞増殖アッセイが下記の通り行われた。要するに、CMFDA染色されたCOV434−AMHRIIが、10μg/mlの無関係のmAb R565、又は抗AMHRII FcKO、又は抗AMHRII 3C23K mAbと共に、4℃で1時間処置され、そして染色されていないMDM2と共に4日間インキュベートされた後、MDM2:T細胞として1:8の比で、CD3/CD28 Dynabeadによって、事前に活性化された、CellTrace Violet(Molecular Probes(登録商標)、Life technologies社(商標))染色されたT細胞が添加された。4日間の追加のインキュベーション期間の後、細胞が採取され、そしてフローサイトメトリー分析前に、抗CD8 PerCP、CD11b PE−Cy7、及びCD4 AF647(BD Pharmingen(登録商標))で染色された。抗体染色前に、Fixable Viability Dye eFluor(登録商標)506(eBioscience(登録商標))染色することによって、死細胞が除外された。T細胞増殖が、細胞***に対応するCellTrace Violet希釈物の指標により、CD8+(CD11b−)Tゲート化細胞上で分析された。初期集団内の細胞が経験した細胞***の平均数に等しい***指標値が、FlowJo(TreeStar、バージョン7.6.5)を用いて計算された。初期集団内の細胞が経験した細胞***の平均数に等しい***指標値が計算された。
腫瘍内のマクロファージはT細胞の抗腫瘍活性を抑制する、ということが明らかに確立される。マクロファージの3C23K抗AMHRII抗体との関与が、それらのT細胞抑制機能が変化させるという仮説を本発明者等は立てた。この仮説を裏付ける為に、COV434−AMHRII標的細胞が、無関係のmAb R565、抗AMHRII FcKO、又は抗AMHRII 3C23K mAbのいずれかを用いて処置され、そしてMDMと共に4日間共培養された後、CD3/CD28で事前に活性化されたPBTが添加された。CD8+T細胞増殖が、フローサイトメトリーにより分析された。予想された通り、対照mAb(無関係のアイソタイプ対照R565及びFcKO抗AMHRII mAbs)の存在下で、又は処置の未実施下で、MDMはT細胞増殖に強い障害をもたらした。とりわけ、MDMを介したT細胞免疫抑制は、共培養された腫瘍細胞が3C23K抗AMHRII mAbを用いて処置された場合に、CD8T細胞の***指標値が大きく増加することにより示されるように(図1A)、有意に低下した。
ADCC/ADCPは、mAbでの処置に応じて、マクロファージによって誘発される唯一の機構ではないとかもしれない。腫瘍関連マクロファージは、T細胞の活性化を抑制することが記載されており(Biswas等,2010年,Nat. Immunol.,Vol.11 (n°10):889-896)、及びリンパ球とマクロファージとの間の接触を示す本発明者等のデータは、両方の細胞型間の直接的な相互干渉のアイディアを裏付ける。イン・ビトロ(in vitro)アッセイを使用することによって、3C23KによるFcRの関与が、マクロファージの免疫抑制的表現型を低下させることを本発明者等は見出した。そのような条件では、事前に活性化されたT細胞は、3C23Kが存在しない場合にはブロックされたその増殖能力を取り戻す。治療用mAbが、先天的免疫細胞だけでなく、適応性免疫細胞にも関与することができるという概念は、これまでの試験と整合する。マウス腫瘍モデルにおいて、抗腫瘍抗原Abを用いて処置すると、T細胞を含め、長期生存に必要とされた細胞性免疫応答を誘発することが実証された(Montalvao等,2013年,J Clin Invest,Vol.123:5098-5103;Gul等,2014年,J clin Invest,Vol.124:812-823)。しかしながら、抗腫瘍mAbで処置された癌患者を対象として適応性免疫応答を誘発することはまだ、広範囲にわたり研究されていない。
A.材料及び方法
ヒト単球由来マクロファージの調製
末梢血単核球(PBMC:Peripheral blood mononuclear cells)は、健康な血液ドナーから得られた。
抗体、すなわちR18H2と命名されたハイポフコシル化抗AMHRII、又はFcγ受容体との結合を一切含まないそのFcKOカウンターパート、の10μg/mLの溶液が、4℃で24時間インキュベートすることによって、24ウェルプレート上に吸着された。この実験条件は、抗体がその抗原を認識した状況を模倣した。コーティングされていない抗体は、PBS溶液を用いて洗浄することによって廃棄された。次に、M2型マクロファージ(細胞106個/mLの培養培地)が、抗体でコーティングされた(又は陰性対照の場合はされない)ウェル中、37℃で、1〜3日間インキュベートされた。
抗体と共にインキュベートされたマクロファージが、100ng/mLのLPSによって6又は24時間刺激された後、qRT−PCR又はフローサイトメトリーによってそれぞれ分析された。PDGFα、VEGFβ、HGF、TGFβ、IDO1、IL10、Sepp1、Stab1、FOLR2、CD64a、CD64b、及びCD16a遺伝子の転写が定量され、そしてRPS18、B2M、及びEF1a遺伝子を参照として使用することによって正規化された。
マルチウェルプレート上に吸着された抗体は、マクロファージのFcγ受容体に結合するそれらの能力に依存して、M2型マクロファージを差動的に刺激した。全体として、M2型マクロファージが抗体を一切ないウェル中で培養された際、マーカーの有意な変化は認められなかった。FcKO抗体を用いた際、それらのタンパク質とマクロファージとの非特異的結合に対応する軽微な変化のみが観察された。対照的に、マクロファージがハイポフコシル化R18H2抗体と相互作用した場合に、図3Aに示されているように、3日間のインキュベーション後に減少したM2型マクロファージの特定の典型的なマーカー、例えばSepp1、Stab1、FOLFR2、及びCD163、の明白な減少が減少した。これらの変化は、マクロファージの型が、ハイポフコシル化抗体による刺激の下で変化する可能性があることを強く示唆する。これらの変化は、抗体に結合し且つCD16(図3B)及びCD64(図3C)のようにADCC及び食作用に関与するFcg受容体の増加が伴った。
A.材料及び方法
ヒト単球由来マクロファージ(MDM:Monocyte-Derived Macrophages)の調製
末梢血単核球(PBMC)は、健康な血液ドナーから得られた(Etablissement Francais de Sang社、EFS)。
SKOV−R2+細胞が、10μg/mLの抗AMHRII抗体:GM102(3C23K−YB20とも命名される)、3C23K−CHO、又は3C23K−FcKOと共に4℃で前処理された。標的SKOV−R2+細胞が、BATDA(ビス−アセトキシメチル−2,2’:6’,2’’−テルピリジン−6,6’’−ジカルボキシレートとともに負荷され、L−グルタミン、PS、及び10%の熱失活されたFCSが補充されたDMEM(Gibco社)中で再懸濁され、そしてエフェクター細胞(ヒトマクロファージ)に1:1の比で、37℃で4時間添加された。
SKOV−R2+細胞が、CellTraceTM Violet細胞増殖キット(Molecular Probes(商標)、Life technology社)で染色され、L−グルタミン、PS、及び10%の熱失活されたウシ胎仔血清(FCS、Sigma社)が補充されたダルベッコ変法イーグル培地(DMEM、Gibco社)中で再懸濁され、そして3つの抗AMHRII抗体のそれぞれが存在する中、1:1の比で、各型のヒトマクロファージに添加された。
受容体発現(CD11b、CD163、CD36、CD206、CD14、CD16、CD32、CD64、CD80、CD282)が、(i)分化させた後、及び(ii)分化させたヒトマクロファージとSKOV−R2+腫瘍細胞(異なる抗AMHRII抗体を用いて処置された)との間で3日間共培養した後に、ヒトマクロファージの膜において、フローサイトメトリーによって評価された。
ヒトT細胞が、製造業者のプロトコールにより推奨されるように、ネガティブセレクションPanT細胞分離キット(Macs Miltenyi社)を使用してPBMCから分離された。分離後、細胞はCellTraceTM Violet細胞増殖キット(Molecular Probes(商標)、Life technology社)で染色され、L−グルタミン、PS、及び10%の熱失活されたFCSが補充されたRPMI1640媒体(Gibco社)中で再懸濁され、そしてヒトマクロファージ+SKOV−R2+腫瘍細胞(上記の異なる抗AMHRII抗体で処置された)の共培養物中に、1:8の比で、4日間添加された。
サイトカイン(IL−1β、IL−2、IL−6、IL−10、IL−12、IL−23、TNF−α、及びTGF−β)、及びケモカイン(CCL2、CCL4、CCL5、CXCL9、及びCXCL10)の放出が、(i)分化したヒトマクロファージの上清、(ii)分化したヒトマクロファージ及びSKOV−R2+腫瘍細胞(異なる抗AMHRII抗体で処置された)との3日間の共培養後の上清、及び(iii)この共培養物+T細胞の追加の4日間後の上清において数値化された。
全ての実験が、3人の異なる独立した健常ドナーからのPBMCを用いて行われた。(M−CSF及びIL−10の添加による)未分化マクロファージ又はTAM様に分化したマクロファージの存在下で測定されたADCCは、不活性な対照として使用された3C23K−CHO又は3C23K−FcKOと比較して、3C23K−YB20低フコース抗体において明らかにより高いことがわかった。TAM様におけるデータが図4Aに提示されている。この細胞溶解活性は、TAM様マクロファージと4日間共インキュベーションした後の腫瘍細胞の減少を、少なくとも部分的に説明しうる。この減少はまた、図4Bに示されているように、3C23K−CHOよりも3C23K YB20において高かった。
A.材料及び方法
同じ組織切片における複数の標的を識別する為に、TSAに基づくマルチプレックス免疫蛍光検査法が、この試験で使用される。チラミドシグナル増幅法(TSA:Tyramide Signal Amplification)は、誘導体化されたチラミドを使用する、特許取得済の触媒式レポーター沈着(CARD:catalyzed reporter deposition)技術に基づく。少量の過酸化水素の存在下で、固定化HRPは、標識された基質(チラミド)を短命で極めて反応性の中間体に変換する。次に、活性化された基質分子は、隣接するタンパク質の電子の豊富な領域と非常に急速に反応し、そしてその領域と共有結合する。活性化されたチラミド分子のこの結合は、活性性HRP酵素が結合する部位のすぐ隣でのみ生ずる。標識されたチラミドの複数の沈着が非常に短時間の(一般的に3〜10分内)うちに生ずる。標識のその後の検出が、シグナルの効率的に大規模な増幅をもたらす。この技法の長所は、同じ種内で生成された複数の一次抗体が、同一の組織スライド上で検出可能である点である。TSA−蛍光色素が析出した場合に、各反応が停止される。これは、5つの標的に達するまで反復可能である。本発明者等の研究室では、Ventana Discovery ULTRA自動スライド染色装置が、該手順を自動化する為に利用可能である。この装置は、FFPE組織スライドの効率的で再現性のあるウォークアウェイ染色(walk-away staining)を可能にする。
リンパ球の為の、サイトケラチン(CK)、CD3、CD4、CD8、FoxP3
マクロファージの為の、CK、CD14、HLADR、CD206、及び/又はCD163
樹状細胞、多形核細胞、ナチュラルキラー細胞の為の、CK、CD56、CD15、グランザイム、DCランプ
免疫細胞に対するエフェクター細胞の為の、CK、CD45、CD16、CD32、及びCD64。
1.抗CD3クローン2GV6、抗CD4クローンSP35、抗CD8クローンC8/144B、抗FoxP3クローンD2W8E、及び抗CKクローンカクテルAE1/AE3
2.抗CD14クローンEPR3653、抗CD68クローンKP−1、抗CD163クローンMRQ−26、抗MHC−IIクローンEPR11226、及び抗CKクローンカクテルAE1/AE3
3.抗CD16クローンSP175、ポリクロナール抗グランザイムB、抗CD8クローンC8/144B、及び抗NKp46
4.抗CD15クローンMMA、抗CD64クローン3D3、ポリクロナール抗CD206、及び抗LAMP3クローン13A205。
GM102の第I相試験の間、幾つかの細胞型の存在が、マルチプレックス蛍光染色法及びFFPEペア化及びベースライン卵巣癌生検分析法を使用して調査された。該マルチプレックス染色は、免疫浸潤物、及び単球/マクロファージ分化の評価、及び食細胞活性を対象とした。ベースラインサンプルが、GM102の7〜15日前に生検採取され、そして第2の生検が、処置の1.5カ月後に行われた。
A.材料及び方法
GM102の第I相試験において、4時点での5mLの血液のサンプリングが、漸増コホートの各患者について計画された。該時点は、1日目の初回GM102注入の前(C1J1−SOIと命名される)、及び初回GM102注入終了時(C1J1−EO1と命名される)、15日目の第2回GM102注入前(C1J15−SOI)、及び定常状態、すなわち57日目の第2回28日サイクルの終了時(C3J1−SOI)である。
*サンプルは、2017年2月9日にEOIにおいて採取され、そして翌日、LIOにて受領された。
**サンプルは、2017年5月29日にEOIにおいて採取され、そして翌日、LIOにて受領された。
1. Aniosを用いて血液チューブを拭き取ることによって、該血液チューブを殺菌する。
2. 15mLのフィコールを事前充填された50mLチューブを取り出し、35mLの希釈された血液を、フィコール上に混合しないようにゆっくりと積層する−2層は明確に分離されていること。(それ以外の体積の場合、希釈血液:フィコールの比を約2/3に維持する)。
3. チューブを密閉し、400g、室温(RT)で20分間、遠心分離する、ブレーキはOFF。
4. 無菌の単回使用の10mLピペットを使用して単核球層(リング)を回復させ、新しい50mLチューブに移す(任意的に:上部相は、リングを回復させる前に廃棄されることができる)。
5. PBSを最大50mL添加し、そして800RPM、15℃で15分間、遠心分離する。
6. ピペットを使用して速やかに上清を取り出し、底部に至る前の3mLで停止する。
7. 衝撃を与えてペレットを再懸濁する。
8. 50mlのPBSを残りの細胞ペレット上に添加し、混合して完全に再懸濁する。
9. 300g、15℃で10分間遠心分離する。
10.チューブを外して、1又は2mLのPBSを添加して細胞をカウントする。
1. 96ウェルプレート内に90μLのBlue Hayemを配置し、10μLの予め再懸濁されたペレットを添加して、PBMCのみをカウントする。
2. 96ウェルプレート内に90μLのBlue Trypanを配置し、10μLの予め再懸濁されたペレットを添加して、生存細胞のみをカウントする。
3. Malassezのスライド上で細胞をカウントし、5〜10百万個の生存細胞をハイクローン中で凍結する(1mL/クライオチューブ(cryotubes))。
4. クライオチューブを「Mr Freeze」ボックス内に配置し、それを少なくとも24時間、−80℃に置いた後、それをGamamabs−GM102のボックス内の窒素タンク中に移す。
上記の各マーカーが、処置に沿って測定及び分析された。テストされた5人の患者において、循環細胞(Ncell、単球、好中球、好酸球、及びT細胞CD4+、CD8+、及びTreg)の主要な免疫集団について有意な変化は識別されなかった。
A.材料及び方法
GM102の第I相試験において、4時点での5mLの血液のサンプリングが、漸増コホートの各患者について計画された。該時点は、1日目の初回GM102注入の前(C1J1−SOIと命名される)、及び初回GM102注入終了時(C1J1−EO1と命名される)、15日目の第2回GM102注入前(C1J15−SOI)、及び定常状態、すなわち57日目の第2回28日サイクルの終了時(C3J1−SOI)である。
3C23Kの第1回注入前のT細胞、NK細胞、及び単球のパーセンテージ(%)は患者間で異なることがわかり、患者間の様々な免疫能力を示す。処置の期間中及びその後に、T細胞及びNK細胞集団において顕著な変化は観察されなかった。対照的に、単球サブセットにおいて変化が観察された。
Claims (14)
- 癌関連免疫抑制の処置における免疫抑制阻害剤としての使用の為の、糖鎖改変されたFcフラグメントを有する化合物。
- ハイポフコシル化Fcフラグメント担持化合物からなる、請求項1に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- 配列番号70の2つのアミノ酸鎖を有する、請求項1又は2に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- 糖鎖改変抗体である、請求項1〜3のいずれか1項に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- 前記糖鎖改変抗体が、腫瘍抗原に対して向けられたものである、請求項4に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- 前記腫瘍抗原が、HER2、HER3、HER4、及びAMHRIIからなる群から選択される、請求項5に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- 前記糖鎖改変抗体が、
(i)下記を含む、糖鎖改変された3C23K抗AMHRII抗体:
a)配列番号2を含む軽鎖及び配列番号4を含む重鎖(リーダーを有さない3C23 VL配列及びVH配列);
b)配列番号6を含む軽鎖及び配列番号8を含む重鎖(リーダーを有さない3C23K VL配列及びVH配列);
c)配列番号10を含む軽鎖及び配列番号12を含む重鎖(リーダーを有さない3C23 軽鎖及び重鎖);
d)配列番号14を含む軽鎖及び配列番号16を含む重鎖(リーダーを有さない3C23K 軽鎖及び重鎖)、
(ii)i)配列番号63の重鎖可変領域と(ii)配列番号64の軽鎖可変領域とを含む抗HER3 9F7F11糖鎖改変抗体、
(iii)(i)配列番号65の重鎖可変領域と(ii)配列番号66の軽鎖可変領域とを含む抗HER3 H4B121糖鎖改変抗体、並びに、
(iv)(i)配列番号67の重鎖可変領域と(ii)配列番号68の軽鎖可変領域とを含む抗HER4 HE4B33糖鎖改変抗体、
からなる群から選択される、請求項4〜6のいずれか1項に記載の、糖鎖改変されたFcフラグメントを有する化合物。 - 前記癌処置が、個体に、抑制性免疫チェックポイントタンパク質阻害剤をさらに投与することを含む、請求項1〜7のいずれか1項に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- 前記抑制性免疫チェックポイントタンパク質阻害剤が、PD−1、PD−L1、PD−L2、BTLA、CTLA−4、A2AR、B7−H3(CD276)、B7−H4(VTCN1)、IDO、KIR、LAG3、TIM−3及びVISTAの阻害剤からなる群から選択される、請求項8に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- 前記阻害剤が、前記抑制性免疫チェックポイントタンパク質に対して向けられた抗体、又はその抗原結合性フラグメントからなる、請求項9に記載の、糖鎖改変されたFcフラグメントを有する化合物。
- (i)請求項1〜10のいずれか1項に記載された、糖鎖改変されたFcフラグメントを有する化合物、及び(ii)抑制性免疫チェックポイントタンパク質阻害剤を含む医薬組成物。
- 前記糖鎖改変されたFcフラグメントを有する化合物が、請求項6又は7に記載された、腫瘍抗原に対して向けられた、糖鎖改変抗体である、請求項11に記載の医薬組成物。
- 前記抑制性免疫チェックポイントタンパク質阻害剤が、PD−1、PD−L1、PD−L2、BTLA、CTLA−4、A2AR、B7−H3(CD276)、B7−H4(VTCN1)、IDO、KIR、LAG3、TIM−3及びVISTAの阻害剤からなる群から選択される、請求項11又は12に記載の医薬組成物。
- 前記抑制性免疫チェックポイントタンパク質阻害剤が、前記抑制性免疫チェックポイントタンパク質に対して向けられた抗体、又はその抗原結合性フラグメントからなる、請求項11〜13のいずれか1項に記載の医薬組成物。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008539753A (ja) * | 2005-05-09 | 2008-11-20 | グリクアート バイオテクノロジー アクチェンゲゼルシャフト | 修飾fc領域およびfc受容体との結合変更を有する抗原結合分子 |
JP2008541770A (ja) * | 2005-06-03 | 2008-11-27 | ジェネンテック・インコーポレーテッド | 改変したフコシル化レベルを有する抗体の産生方法 |
US20140141019A1 (en) * | 2011-05-13 | 2014-05-22 | Inserm (Institut Nationalde La Sente Et De La Recherche Medicale) | Antibodies against her3 |
JP2015506341A (ja) * | 2011-12-23 | 2015-03-02 | ラボラトワール フランセ ドゥ フラクションマン エ デ バイオテクノロジーズLaboratoire Francais Du Fractionnement Et Des Biotechnologies | ヒト抗ミュラー管ホルモンii型受容体と結合する抗体を含む新規医薬組成物 |
WO2015159253A1 (fr) * | 2014-04-16 | 2015-10-22 | Gamamabs Pharma | Anticorps humain anti-her4 |
JP2016516800A (ja) * | 2013-04-22 | 2016-06-09 | グリコトープ ゲーエムベーハー | フコシル化が少ない抗egfr抗体による抗がん処置 |
JP2016536988A (ja) * | 2013-11-07 | 2016-12-01 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | ニューレグリンに対して非競合的でアロステリックな抗ヒトher3抗体及びその使用 |
US20170035903A1 (en) * | 2015-08-07 | 2017-02-09 | Gamamabs Pharma | Antibodies, antibody drug conjugates and methods of use |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT1071700E (pt) | 1998-04-20 | 2010-04-23 | Glycart Biotechnology Ag | Modificação por glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
PT1914244E (pt) | 1999-04-09 | 2013-07-26 | Kyowa Hakko Kirin Co Ltd | Processo para regular a actividade de moléculas funcionais sob o ponto de vista imunológico |
DE60139720D1 (de) | 2000-06-28 | 2009-10-08 | Glycofi Inc | Verfahren für die Herstellung modifizierter Glykoproteine |
US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
EP2339004B1 (en) | 2002-03-19 | 2015-02-25 | Stichting Dienst Landbouwkundig Onderzoek | Optimizing glycan processing in plants |
EP1791868B1 (en) | 2004-07-01 | 2011-02-23 | Novo Nordisk A/S | Antibodies binding to receptors kir2dl1, -2, 3 but not kir2ds4 and their therapeutic use |
CA2970873C (en) | 2005-05-09 | 2022-05-17 | E. R. Squibb & Sons, L.L.C. | 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 |
AU2007205939B2 (en) | 2006-01-17 | 2012-12-13 | Synthon Biopharmaceuticals B.V. | Compositions and methods for humanization and optimization of N-glycans in plants |
US7846724B2 (en) | 2006-04-11 | 2010-12-07 | Hoffmann-La Roche Inc. | Method for selecting CHO cell for production of glycosylated antibodies |
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 |
EP3222634A1 (en) | 2007-06-18 | 2017-09-27 | Merck Sharp & Dohme B.V. | Antibodies to human programmed death receptor 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 |
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 |
PE20120341A1 (es) | 2008-12-09 | 2012-04-24 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t |
EA201270228A1 (ru) | 2009-07-31 | 2012-09-28 | Медарекс, Инк. | Полноценные человеческие антитела к btla |
CN102666581A (zh) | 2009-08-31 | 2012-09-12 | 艾普利穆恩公司 | 用于抑制移植物排斥的方法和组合物 |
KR101573109B1 (ko) | 2009-11-24 | 2015-12-01 | 메디뮨 리미티드 | B7―h1에 대한 표적화된 결합 물질 |
US8802091B2 (en) | 2010-03-04 | 2014-08-12 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
FR2959994B1 (fr) * | 2010-05-12 | 2012-08-24 | Lfb Biotechnologies | Nouveaux anticorps humanises 12g4 mutes et leurs fragments diriges contre le recepteur humain de l'hormone anti-mullerienne de type ii |
WO2013006490A2 (en) | 2011-07-01 | 2013-01-10 | Cellerant Therapeutics, Inc. | Antibodies that specifically bind to tim3 |
AU2012296613B2 (en) | 2011-08-15 | 2016-05-12 | Amplimmune, Inc. | Anti-B7-H4 antibodies and their uses |
WO2013067492A1 (en) | 2011-11-03 | 2013-05-10 | The Trustees Of The University Of Pennsylvania | Isolated b7-h4 specific compositions and methods of use thereof |
CA2949081C (en) * | 2014-05-16 | 2023-03-07 | Baylor Research Institute | Methods and compositions for treating autoimmune and inflammatory conditions |
US9630575B2 (en) | 2015-09-30 | 2017-04-25 | GM Global Technology Operations LLC | Panel assembly with noise attenuation system |
-
2018
- 2018-05-29 CA CA3064333A patent/CA3064333A1/en active Pending
- 2018-05-29 US US16/617,136 patent/US20200148777A1/en active Pending
- 2018-05-29 EP EP18727015.2A patent/EP3630826A1/en active Pending
- 2018-05-29 MX MX2019014192A patent/MX2019014192A/es unknown
- 2018-05-29 BR BR112019025352A patent/BR112019025352A8/pt unknown
- 2018-05-29 KR KR1020197038406A patent/KR20200031571A/ko not_active Application Discontinuation
- 2018-05-29 JP JP2019565843A patent/JP2020521780A/ja active Pending
- 2018-05-29 CN CN201880048764.4A patent/CN111108123A/zh active Pending
- 2018-05-29 WO PCT/EP2018/064081 patent/WO2018219956A1/en active Application Filing
-
2022
- 2022-09-26 JP JP2022153137A patent/JP2023073965A/ja active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008539753A (ja) * | 2005-05-09 | 2008-11-20 | グリクアート バイオテクノロジー アクチェンゲゼルシャフト | 修飾fc領域およびfc受容体との結合変更を有する抗原結合分子 |
JP2008541770A (ja) * | 2005-06-03 | 2008-11-27 | ジェネンテック・インコーポレーテッド | 改変したフコシル化レベルを有する抗体の産生方法 |
US20140141019A1 (en) * | 2011-05-13 | 2014-05-22 | Inserm (Institut Nationalde La Sente Et De La Recherche Medicale) | Antibodies against her3 |
JP2015506341A (ja) * | 2011-12-23 | 2015-03-02 | ラボラトワール フランセ ドゥ フラクションマン エ デ バイオテクノロジーズLaboratoire Francais Du Fractionnement Et Des Biotechnologies | ヒト抗ミュラー管ホルモンii型受容体と結合する抗体を含む新規医薬組成物 |
JP2016516800A (ja) * | 2013-04-22 | 2016-06-09 | グリコトープ ゲーエムベーハー | フコシル化が少ない抗egfr抗体による抗がん処置 |
JP2016536988A (ja) * | 2013-11-07 | 2016-12-01 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | ニューレグリンに対して非競合的でアロステリックな抗ヒトher3抗体及びその使用 |
WO2015159253A1 (fr) * | 2014-04-16 | 2015-10-22 | Gamamabs Pharma | Anticorps humain anti-her4 |
US20170035903A1 (en) * | 2015-08-07 | 2017-02-09 | Gamamabs Pharma | Antibodies, antibody drug conjugates and methods of use |
Non-Patent Citations (1)
Title |
---|
ONCOTARGET, vol. 8, no. 23, JPN6022011433, 2017, pages 37061 - 37079, ISSN: 0004734496 * |
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US20200148777A1 (en) | 2020-05-14 |
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