JP2022523656A - T細胞リンパ腫の処置 - Google Patents
T細胞リンパ腫の処置 Download PDFInfo
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Abstract
Description
本出願は、2019年1月22日に提出された米国仮特許出願第62/795,194号明細書の利益を主張し、これは、任意の図面を含め、その全体が参照によって本明細書に援用される。
本出願は、電子形式の配列表と共に提出される。配列表は、サイズが54KBである、2020年1月14日に作られた「KIR-9 PCT_ST25」というタイトルのファイルとして提供される。配列表の電子形式の情報は、その全体が参照により本明細書に組み込まれる。
- カルボプラチンと組み合わせて、白金ベースの療法の終了の少なくとも6ヵ月後に再発した進行卵巣癌の処置のため、
- パクリタキセルと組み合わせて、アントラサイクリンが臨床上禁忌である場合を除いて、先に行われたアントラサイクリン含有補助化学療法に失敗した後の転移性乳癌の第一選択処置のため、
- シスプラチンと組み合わせて、非小細胞肺癌の処置のため、及び
- 膵臓癌の処置のための単剤として。
- 原発腫瘍の完全切除を受けたことがある患者における病期III結腸癌の補助的処置、及び
- 進行結腸直腸癌の処置。
KIR3DL2ポリペプチドに結合する抗体の活性を強化するために、悪性T細胞の表面でのKIR3DL2発現を誘発するか又は増加させる薬剤の投与を通した個人におけるTCLの処置及び予防において有用な方法が本明細書に記載される。本明細書に記載される治療レジメン及び治療法は、種々のT細胞リンパ腫、特にCD4+T細胞リンパ腫に使用することができる。任意の態様において、TCLは、表面にKIR3DL2を発現する悪性細胞によって特徴付けられるTCLであると指定することができる。
- 抗KIR3DL2抗体の少なくとも1用量、任意選択で少なくとも2用量(例えば、毎週、2週間ごと、4週間ごと)、
- ゲムシタビンの少なくとも1用量、任意選択で少なくとも2用量、任意選択で、ゲムシタビンは、約800~1000mg/m2の用量で投与され、任意選択で、ゲムシタビンは、2週間毎に1回又は繰り返される3週間サイクルの1日目及び8日目に投与される、及び
- オキサリプラチンの少なくとも1用量、任意選択で少なくとも2用量、任意選択で、オキサリプラチンは、約75~130mg/m2の用量で投与され、任意選択で、オキサリプラチンは、2週間毎に1回又は3週間毎に1回(例えば、すなわち繰り返される3週間サイクルの1日目に)投与される。
一実施形態において、オキサリプラチン及びゲムシタビンは、それぞれ2週間ごとに1回、任意選択でさらに同じ日に投与される。別の実施形態において、オキサリプラチン及びゲムシタビンは、それぞれ3週間毎に投与され、オキサリプラチンは、3週間の期間の1日目に投与され、ゲムシタビンは、3週間の期間の1日目及び8日目に投与される。
(a)750mgの抗KIR3DL2抗体及び(i)75~130mg/m2の白金製剤(例えば、オキサリプラチン)又は(ii)800~1200mg/m2のゲムシタビン;
(b)1~10mg/kg又は750mgの抗KIR3DL2抗体及び75~130mg/m2のオキサリプラチン;
(c)1~10mg/kg又は750mgの抗KIR3DL2抗体及び800~1200mg/m2のゲムシタビン;
(d)1~10mg/kg又は750mgの抗KIR3DL2抗体、75~100mg/m2のオキサリプラチン及び800~1000mg/m2のゲムシタビン;
(e)1~10mg/kg又は750mgの抗KIR3DL2抗体、100~130mg/m2のオキサリプラチン及び800~1000mg/m2のゲムシタビン。
(i)抗KIR3DL2抗体を含有する医薬組成物及びゲムシタビンを含有する医薬組成物;
(ii)抗KIR3DL2抗体を含有する医薬組成物及び白金製剤(例えば、オキサリプラチン)を含有する医薬組成物;
(iii)抗KIR3DL2抗体を含有する医薬組成物、白金製剤(例えば、オキサリプラチン)を含有する医薬組成物及びゲムシタビンを含有する医薬組成物;
(iv)抗KIR3DL2抗体を含有する第1の医薬組成物並びに前記抗KIR3DL2抗体を、白金製剤(例えば、オキサリプラチン)及び/又はゲムシタビンと一緒に投与するための指示書;
(v)白金製剤(例えば、オキサリプラチン)及び/又はゲムシタビンを含有する医薬組成物並びに前記組成物を抗KIR3DL2抗体と一緒に投与するための指示書;
(vi)白金製剤(例えば、オキサリプラチン)を含有する医薬組成物並びに前記組成物を抗KIR3DL2抗体(及び任意選択でさらにゲムシタビン)と一緒に投与するための指示書;
(vii)ゲムシタビンを含有する医薬組成物並びに前記組成物を抗KIR3DL2抗体(及び任意選択でさらに白金製剤(例えば、オキサリプラチン))と一緒に投与するための指示書。
(a)配列番号32若しくは48~51のいずれかにおいて示される配列を有する重鎖可変領域のH-CDR1、H-CDR2及びH-CDR3ドメイン並びに配列番号33若しくは43~47において示される配列を有する軽鎖可変領域のL-CDR1、L-CDR2及びL-CDR3ドメインを含む、ある用量の抗KIR3DL2抗体;及び/又は
(b)ある用量の白金製剤(例えば、オキサリプラチン)及び/若しくはある用量のゲムシタビン;並びに
(c)任意選択で、本明細書に記載される任意の方法において、前記抗KIR3DL2抗体及び/若しくは前記白金製剤(例えば、オキサリプラチン)及び/若しくはゲムシタビンを使用するための指示書。
KIR3DL2(CD158k)は、開示が参照により本明細書に組み込まれるPende et al.(1996)J.Exp.Med.184:505-518において記載される約140kDの3つのIgドメイン分子のジスルフィド結合ホモ二量体である。いくつかの対立遺伝子変異体がKIR3DL2ポリペプチドについて報告されており、これらのそれぞれは、用語KIR3DL2によって包含される。成熟ヒトKIR3DL2(allele *002)のアミノ酸配列は、下記に配列番号1において示され、21アミノ酸残基リーダー配列が省かれたGenbank受入番号AAB52520に対応する。
AZ158は、ヒトKIR3DL2ポリペプチド及びヒトKIR3DL1ポリペプチドに結合する(国際公開第2010/081890号パンフレットを参照されたい)。AZ158のVHは、下記に示され、CDR1、2及び3にそれぞれ下線を引く。
(a)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る配列番号5の重鎖可変領域;並びに/又は
(b)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る配列番号6の軽鎖可変領域;並びに/又は
(c)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る配列番号5の重鎖可変領域;及び1つ以上のこれらのアミノ酸が異なるアミノ酸によって置換され得る配列番号6の軽鎖可変領域;並びに/又は
(d)任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号7~9、10~11及び12においてそれぞれ示される重鎖CDR1、2及び3(HCDR1、HCDR2、HCDR3)アミノ酸配列;並びに/又は
(e)任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号13、14若しくは15においてそれぞれ示される軽鎖CDR1、2及び3(LCDR1、LCDR2、LCDR3)アミノ酸配列;並びに/又は
(f)任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号7、8若しくは9、10若しくは11及び12においてそれぞれ示される重鎖CDR1、2及び3(HCDR1、HCDR2、HCDR3)アミノ酸配列;及び1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号13、14若しくは15において示される軽鎖CDR1、2及び3(LCDR1、LCDR2、LCDR3)アミノ酸配列;並びに/又は
(g)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号5のアミノ酸配列を有する可変領域と少なくとも60%、70%、80%、85%、90%若しくは95%同一である重鎖可変領域;並びに/又は
(h)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号6のアミノ酸配列を有する可変領域と少なくとも60%、70%、80%、85%、90%若しくは95%同一である軽鎖可変領域を含む、ヒトKIR3DL2に結合する抗体が提供される。
(a)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る配列番号16の重鎖可変領域;並びに/又は
(b)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る配列番号17の軽鎖可変領域;並びに/又は
(c)1つ以上のアミノ酸残基が異なるアミノ酸によって置換され得る配列番号16の重鎖可変領域;及び1、2、3つ若しくはそれを超えるこれらのアミノ酸が異なるアミノ酸によって置換され得る配列番号17の軽鎖可変領域;並びに/又は
(d)任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号18、19若しくは20、21若しくは22及び23においてそれぞれ示される重鎖CDR1、2及び3(HCDR1、HCDR2、HCDR3)アミノ酸配列;並びに/又は
(e)任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号24、25及び26おいて示される軽鎖CDR1、2及び3(LCDR1、LCDR2、LCDR3)アミノ酸配列;並びに/又は
(f)任意のCDRの1つ以上のアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号18、19若しくは20、21若しくは22及び23においてそれぞれ示される重鎖CDR1、2及び3(HCDR1、HCDR2、HCDR3)アミノ酸配列;及び任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号24、25及び26において示される軽鎖CDR1、2及び3(LCDR1、LCDR2、LCDR3)アミノ酸配列;並びに/又は
(g)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号16のアミノ酸配列を有する可変領域と少なくとも60%、70%、80%、85%、90%若しくは95%同一である重鎖可変領域;並びに/又は
(h)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号17のアミノ酸配列を有する可変領域と少なくとも60%、70%、80%、85%、90%若しくは95%同一である軽鎖可変領域
を含む、ヒトKIR3DL2に結合する抗体が提供される。
(a)任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号34、35若しくは36(HCDR1)、37若しくは38(HCDR2)及び39(HCDR3)においてそれぞれ示される重鎖CDR1、2及び3(HCDR1、HCDR2、HCDR3)アミノ酸配列;並びに/又は
(b)任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号40、41及び42おいて示される軽鎖CDR1、2及び3(LCDR1、LCDR2、LCDR3)アミノ酸配列;並びに/又は
(c)任意のCDRの1つ以上のアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号34、35若しくは36(HCDR1)、37若しくは38(HCDR2)及び39(HCDR3)においてそれぞれ示される重鎖CDR1、2及び3(HCDR1、HCDR2、HCDR3)アミノ酸配列;及び任意のCDRの1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号40、41及び42において示される軽鎖CDR1、2及び3(LCDR1、LCDR2、LCDR3)アミノ酸配列;並びに/又は
(d)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号32又は48~51のアミノ酸配列を有する可変領域と少なくとも60%、70%、80%、85%、90%若しくは95%同一である重鎖可変領域;並びに/又は
(e)1、2、3つ若しくはそれを超えるアミノ酸残基が異なるアミノ酸によって置換され得る、配列番号33又は43~47のアミノ酸配列を有する可変領域と少なくとも60%、70%、80%、85%、90%若しくは95%同一である軽鎖可変領域
を含む、ヒトKIR3DL2を結合する抗体が提供される。
別の態様において、本発明の処置の方法で使用される抗KIR3DL2抗体は、ヒト化抗体、例えば下記の表Bにおいて示される2B12及び10G5可変領域から選択されるVH及びVLを有するヒト化2B12又は10G5抗体である。
(a)配列番号34、35又は36のアミノ酸配列を含むCDR-H1;
(b)配列番号37又は38のアミノ酸配列を含むCDR-H2;
(c)配列番号39のアミノ酸配列を含むCDR-H3;
(d)配列番号40のアミノ酸配列を含むCDR-L1;
(e)配列番号41のアミノ酸配列を含むCDR-L2;
(f)配列番号42のアミノ酸配列を含むCDR-L3;及び
(g)ヒトフレームワーク配列。
(a)配列番号49のアミノ酸配列を含む重鎖可変領域、及び
(b)配列番号44のアミノ酸配列を含む軽鎖可変領域
を含む。
(a)配列番号49のアミノ酸配列を含む重鎖可変領域、及び
(b)配列番号45のアミノ酸配列を含む軽鎖可変領域
を含む。
(a)配列番号58のアミノ酸配列を含む重鎖可変領域、及び
(b)配列番号53のアミノ酸配列を含む軽鎖可変領域
を含む。
(a)配列番号59のアミノ酸配列を含む重鎖可変領域、及び
(b)配列番号53のアミノ酸配列を含む軽鎖可変領域
を含む。
化学療法剤が宿主免疫系に負に影響し、その結果として、ADCCを媒介する治療抗体の効能を阻害し得ることが知られている。その結果として、本発明者らは、化学療法剤が、ヒトIgG1アイソタイプ並びにそれぞれ配列番号49及び44において示されるVH及びVLアミノ酸配列を有するヒト化2B12抗体ラクタマブのNK細胞媒介性ADCC活性に影響するかどうかを評価することを試みた。化学療法剤を、単独で又は組み合わせて、同種異系NK細胞及びKIR3DL2発現セザリー症候群細胞系(Hut78)と共に、濃度を増加させながらの抗KIR3DL2抗体の存在下においてインビトロ細胞傷害(ADCC)アッセイに追加した。
HUT78 CTCL細胞系に対する抗KIR3DL2抗体誘発性のADCCの増強について考え得る理由について調べるために、本発明者らは、KIR3DL2発現がインビトロにおいて同じ化学療法薬によって調整することができるかどうかを評価した。
完全に機能的なNK細胞及びマクロファージを保持する免疫不全マウス株のCB17-SCIDマウスにおける異種移植片モデルである。加えて、マウスFc受容体は、ヒトFcに有効に結合し、マウスエフェクター細胞がヒト化mAbによって動員され、ADCC又はADCPを実行することをインビボにおいて可能にする。B-NHL細胞系RAJIを、KIR3DL2(RAJI-KIR3DL2)を安定して発現するようにトランスフェクトし、トランスフェクタントをIVによってSCIDマウスに接種し(5×106細胞)、それにより播種腫瘍モデルがもたらされた。最初に、ゲムシタビン及びオキサリプラチンの個々の用量をこの異種移植片モデルにおいて確立した。しかしながら、ゲムシタビン及びオキサリプラチンは、ヒトにおいて一緒に使用することができるが、これらのマウスにおいて、活性であるが、忍容性であるように組み合わせることができるゲムシタビン及びオキサリプラチンの用量を見出すことは、不可能であった。その結果として、抗KIR3DL2抗体(ラクタマブ)は、ゲムシタビン又はオキサリプラチンと別々に組み合わせた。
- アイソタイプコントロールmAb、
- 抗KIR3DL2抗体(ラクタマブ)、
- ゲムシタビン(50mg/kg)
- オキサリプラチン(5mg/kg)、
- 抗KIR3DL2抗体(ラクタマブ)+ゲムシタビン(50mg/kg)、又は
- 抗KIR3DL2抗体(ラクタマブ)+オキサリプラチン(5mg/kg)。
Claims (35)
- TCLの処置において使用するための、KIR3DL2ポリペプチドに結合する抗体であって、ゲムシタビンと組み合わせて使用される抗体。
- TCLの処置において使用するための、KIR3DL2ポリペプチドに結合する抗体であって、白金製剤、任意選択でオキサリプラチンと組み合わせて使用される抗体。
- 前記処置は、(a)KIR3DL2ポリペプチドに結合する抗体、(b)ゲムシタビン、及び(c)白金製剤、任意選択でオキサリプラチンのそれぞれの有効量を投与することを含む、請求項1又は2に記載の抗体。
- ゲムシタビンは、2週間ごとに1回、800~1000mg/m2の用量で投与される、請求項1~3のいずれか一項に記載の抗体。
- オキサリプラチンは、2週間ごとに1回、75~100mg/m2の用量で投与される、請求項2~4のいずれか一項に記載の抗体。
- オキサリプラチンは、3週間ごとに1回、75~130mg/m2の用量で投与される、請求項2~5のいずれか一項に記載の抗体。
- 1週間当たり1回~4週間ごとに1回投与される、請求項1~6のいずれか一項に記載の抗体。
- 1週間当たり1回投与され、任意選択で第1相において1週間当たり1回投与され、続いて、第2相において2週間ごとに1回又は1ヵ月当たり1回投与される、請求項1~7のいずれか一項に記載の抗体。
- 前記TCLは、末梢T細胞リンパ腫(PTCL)である、請求項1~8のいずれか一項に記載の抗体。
- 前記PTCLは、成人T細胞白血病(ATL)、腸症関連T細胞リンパ腫(EATL)、PTCL-NOS又は未分化大細胞リンパ腫(ALCL)である、請求項9に記載の抗体。
- 1~20mg/kgの用量、任意選択で750mgの用量で投与される、請求項1~10のいずれか一項に記載の抗体。
- 少なくとも1回の投与サイクルを含むレジメンにおいて投与され、前記少なくとも1回のサイクルのそれぞれについて、2、3又は4用量の前記抗KIR3DL2抗体が投与され、及び少なくとも2、3又は4用量のゲムシタビンが投与され、ゲムシタビンは、2週間ごとに1回、800~1000mg/m2の用量で投与される、請求項1~11のいずれか一項に記載の抗体。
- 少なくとも1回の投与サイクルを含むレジメンにおいて投与され、前記少なくとも1回のサイクルのそれぞれについて、2、3又は4用量の前記抗KIR3DL2抗体が投与され、及び少なくとも2、3又は4用量のゲムシタビン及びオキサリプラチンが投与され、オキサリプラチンは、2週間ごとに1回、75~130mg/m2の用量で投与され、及びゲムシタビンは、2週間ごとに1回、800~1000mg/m2の用量で投与される、請求項1~12のいずれか一項に記載の抗体。
- 個人におけるTCLの前記処置は、
a)TCLを有する前記個人内の悪性細胞のKIR3DL2ポリペプチドステータスを決定することと、
b)前記個人が、悪性細胞の表面上に発現されるKIR3DL2ポリペプチドを有すると決定されると、前記白金製剤及び/又はゲムシタビンと組み合わせて、KIR3DL2ポリペプチドに結合する前記抗体を前記個人に投与することと
を含む、請求項1~13のいずれか一項に記載の抗体。 - KIR3DL2ポリペプチドが前記悪性細胞の前記表面上に発現されるかどうかを決定することは、末梢T細胞リンパ腫細胞を含む生物学的サンプルを前記個人から得ることと、前記細胞を、KIR3DL2ポリペプチドに結合する抗体と接触させることと、KIR3DL2を発現する細胞を検出することとを含む、請求項14に記載の抗体。
- 前記白金製剤は、オキサリプラチン、シスプラチン、カルボプラチン、ネダプラチン、フェナントリプラチン、ピコプラチン又はサトラプラチンである、請求項1~15のいずれか一項に記載の抗体。
- ヒトIgG1又はIgG3重鎖Fcドメインを含む、請求項1~16のいずれか一項に記載の抗体。
- KIR3DL2発現細胞のエフェクター細胞媒介性溶解を引き起こすことができ、任意選択でKIR3DL2発現細胞のエフェクター細胞媒介性溶解を媒介する、請求項17に記載の抗体。
- ヒトFcγ受容体への結合を増強するアミノ酸修飾を含む、請求項1~18のいずれか一項に記載の抗体。
- 毒性の薬剤に連結される、請求項1~19のいずれか一項に記載の抗体。
- ヒトKIR3DL2のD0又はD1ドメインに結合する、請求項1~20のいずれか一項に記載の抗体。
- 配列番号1の野生型KIR3DL2ポリペプチドと比較して、残基P179及び/又は残基S181に突然変異を有するKIR3DL2ポリペプチドへの低下した結合を有する、請求項1~21のいずれか一項に記載の抗体。
- 配列番号1の野生型KIR3DL2ポリペプチドと比較して、残基I60及び/又は残基G62に突然変異を有するKIR3DL2ポリペプチドへの低下した結合を有する、請求項1~22のいずれか一項に記載の抗体。
- ヒトKIR3DL2への結合について抗体AZ158、10G5、19H12、2B12又は12B11と競合する、請求項1~23のいずれか一項に記載の抗体。
- (a)配列番号48~51のいずれかの2B12 VHと少なくとも85%同一のアミノ酸配列を含むVHドメイン、及び(b)配列番号43~47のいずれかの2B12 VLと少なくとも85%同一のアミノ酸配列を含むVLドメインを含む、請求項1~24のいずれか一項に記載の抗体。
- (a)配列番号49のアミノ酸配列を含む重鎖可変領域、及び(b)配列番号44又は45のアミノ酸配列を含む軽鎖可変領域を含む、請求項1~25のいずれか一項に記載の抗体。
- 前記KIR3DL2抗体並びに前記白金製剤及び/又はゲムシタビンは、同時に、別々に又は順次投与される、請求項1~26のいずれか一項に記載の使用のための抗体。
- KIR3DL2ポリペプチドに結合し、KIR3DL2発現細胞を除去することができる抗体と組み合わせて、TCLの処置において使用するためのゲムシタビン及び/又は白金製剤を含む医薬組成物。
- 前記処置は、(a)KIR3DL2ポリペプチドに結合し、且つKIR3DL2発現細胞を除去することができる抗体、(b)白金製剤を含む医薬組成物、及び(c)ゲムシタビンを含む医薬組成物のそれぞれの有効量を個人に投与することを含む、請求項28に記載の組成物。
- 前記個人は、末梢T細胞リンパ腫(PTCL)又は皮膚T細胞リンパ腫(CTCL)、任意選択で成人T細胞白血病(ATL)、腸症関連T細胞リンパ腫(EATL)又は未分化大細胞リンパ腫(ALCL)を有する、請求項28又は29に記載の組成物。
- 個人におけるTCLの前記処置は、
a)TCLを有する前記個人内の悪性細胞上のKIR3DL2ポリペプチド発現を評価することと、
b)前記個人が、悪性細胞の表面上に発現されるKIR3DL2ポリペプチドを有すると決定されると、前記白金製剤及び/又はゲムシタビンと組み合わせて、KIR3DL2ポリペプチドに結合する前記抗体を前記個人に投与することと
を含む、請求項28~30のいずれか一項に記載の組成物。 - KIR3DL2ポリペプチドが前記悪性細胞の前記表面上に発現されるかどうかを決定することは、T細胞リンパ腫細胞を含む生物学的サンプルを前記個人から得ることと、前記細胞を、KIR3DL2ポリペプチドに結合する抗体と接触させることと、KIR3DL2を発現する細胞を検出することとを含む、請求項31に記載の組成物。
- 前記白金製剤は、オキサリプラチン、シスプラチン、カルボプラチン、ネダプラチン、フェナントリプラチン、ピコプラチン又はサトラプラチンである、請求項28~32のいずれか一項に記載の組成物。
- KIR3DL2ポリペプチドに結合する前記抗体は、請求項18~26のいずれか一項に記載の抗体である、請求項28~33のいずれか一項に記載の組成物。
- TCLの処置のための、KIR3DL2ポリペプチドに結合する抗体との組み合わせの使用のための抗癌剤の効能又は適合性を予測又は評価する方法であって、前記抗癌剤が悪性T細胞の表面でのKIR3DL2の発現を誘発するか又は増加させることができるかどうかを決定又は評価することを含み、前記抗癌剤が悪性T細胞の表面でのKIR3DL2の発現を誘発するか又は増加させることができるという決定は、前記薬剤が抗KIR3DL2抗体と組み合わせて癌の処置に使用され得ることを示す、方法。
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