JP2020511936A - 新規t細胞受容体およびそれを用いた免疫療法 - Google Patents
新規t細胞受容体およびそれを用いた免疫療法 Download PDFInfo
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- Virology (AREA)
Abstract
Description
a)適切な宿主細胞を提供するステップと、
b)本明細書で開示される発明による抗原認識コンストラクトをコードするコード配列を含んでなる遺伝子コンストラクトを提供するステップと、
c)前記遺伝子コンストラクトを前記適切な宿主細胞に導入するステップと、
d)前記適切な宿主細胞によって前記遺伝子コンストラクトを発現させるステップと
を含んでなる、TAA特異的抗原認識コンストラクトの製造、またはTAA特異的抗原認識コンストラクト発現細胞株の製造方法によっても解決される。
b)細胞を本発明の抗原認識コンストラクトをコードする少なくとも1つのベクターで形質転換して、形質転換細胞を生成するステップと;
c)形質転換細胞を増殖させて、複数の形質転換細胞を生成するステップと;
d)複数の形質転換細胞を前記対象に投与するステップと
を含んでなる、それを必要とする対象においてがんを治療する方法もまた提供される。
b)細胞を本発明の抗原認識コンストラクトをコードするベクターで形質転換して、形質転換細胞を生成するステップと;
c)形質転換細胞を増殖させて、複数の形質転換細胞を生成するステップと;
d)複数の形質転換細胞を前記対象に投与するステップと
を含んでなる、それを必要とする対象においてがんを治療する方法もまた提供される。
b)抗原認識コンストラクト(例えば、TCR)の生物学的サンプルへの結合を検出するステップと
を含んでなる、生物学的サンプルにおいてがんを検出する方法もまた提供される。
項目1:配列番号3、9、15、21、27、および33から選択されるアミノ酸配列と少なくとも50%の配列同一性を有する、少なくとも1つの相補性決定領域(CDR)3を含んでなる抗原認識コンストラクト。
b.項目1〜20のいずれか一項に記載の抗原認識コンストラクトをコードするコード配列を含んでなる遺伝子コンストラクトを提供するステップと、
c.前記遺伝子コンストラクトを前記適切な宿主細胞に導入するステップと、
d.前記適切な宿主細胞によって前記遺伝子コンストラクトを発現させるステップと
を含んでなる、細胞株を発現するTAA特異的抗原認識コンストラクトを製造する方法。
a)細胞を前記対象から単離するステップと;
b)細胞を上記の項目のいずれか一項に記載のTCRをコードするベクターで形質転換して形質転換細胞を生成するステップと;
c)形質転換細胞を増殖させて、複数の形質転換細胞を生成するステップと;
d)複数の形質転換細胞を前記対象に投与するステップと
を含んでなる、それを必要とする対象においてがんを治療する方法。
a)細胞を健常ドナーから単離するステップと;
b)細胞を上記の項目のいずれか一項に記載のTCRをコードするベクターで形質転換して形質転換細胞を生成するステップと;
c)形質転換細胞を増殖させて、複数の形質転換細胞を生成するステップと;
d)複数の形質転換細胞を前記対象に投与するステップと
を含んでなる、それを必要とする対象においてがんを治療する方法。
それぞれ、腫瘍特異的TCR−αおよびTCR−β鎖をコードする3つのDCAF4L2−001特異的TCR(R36P3F9、R52P2G11、およびR53P2A9、表1を参照されたい)を健常ドナーのT細胞から単離し、増幅した。健常ドナーに由来する細胞は、以前記載された方法に従って生体外で刺激し(Walter et al.,2003 J Immunol.,Nov 15;171(10):4974−8)、HLA−A*02多量体を用いて標的特異的細胞を単細胞ソートし、次に引き続くTCR単離のために使用した。例えば、Molecular Cloning a laboratory manual fourth edition by Green and Sambrookに記載されるように、標準法によって5’RACEを通じてTCR配列を単離した。TCR R36P3F9、TCR R52P2G11、およびTCR R53P2A9のαおよびβ可変領域を配列決定し、さらなる機能特性解析のために、発現コンストラクトを遺伝子合成によって作製した。R36P3F9はHLA−A*02陽性ドナーに由来し、R52P2G11およびR53P2A9はHLA−A*02陰性ドナーに由来する(アロ反応性設定)。
TCR R36P3F9(配列番号1〜12)は、HLA−A*02を提示するDCAF4L2−001に対して拘束されている(図4参照)。
TCR R52P2G11(配列番号13〜24)は、HLA−A*02を提示するDCAF4L2−001に対して拘束されている(図5参照)。
TCR R53P2A9(配列番号25〜36)は、HLA−A*02を提示するDCAF4L2−001に対して拘束されている(図6参照)。
Claims (22)
- 配列番号3、9、15、21、27、および33から選択されるアミノ酸配列と少なくとも50%の配列同一性を有する、少なくとも1つの相補性決定領域(CDR)3を含んでなる抗原認識コンストラクト。
- 請求項1に記載の抗原認識コンストラクトであって、前記抗原認識コンストラクトが、配列番号49、および50〜57から選択されるアミノ酸配列を含んでなり、またはそれからなるエピトープに、特異的におよび/または選択的に結合できる、抗原認識コンストラクト。
- 請求項1または2に記載の抗原認識コンストラクトであって、前記抗原認識コンストラクトが、抗体、またはその誘導体もしくは断片、またはT細胞受容体(TCR)、またはその誘導体もしくは断片である、抗原認識コンストラクト。
- 請求項1〜3のいずれか一項に記載の抗原認識コンストラクトであって、前記TCRαまたはγ鎖が、配列番号3、15、および27から選択されるアミノ酸配列と少なくとも50%の配列同一性を有するCDR3を含んでなり;および/または前記TCRβまたはδ鎖が、配列番号9、21、および33から選択されるアミノ酸配列と少なくとも50%の配列同一性を有するCDR3を含んでなる、TCRαまたはγ鎖および/またはTCRβまたはδ鎖を含んでなる、抗原認識コンストラクト。
- 請求項4に記載の抗原認識コンストラクトであって、前記TCRαまたはγ鎖が、配列番号1、13、および25から選択されるアミノ酸配列と少なくとも50%の配列同一性を有するCDR1;および/または配列番号2、14、および26から選択されるアミノ酸配列と少なくとも50%の配列同一性を有するCDR2をさらに含んでなる、抗原認識コンストラクト。
- 請求項4または5に記載の抗原認識コンストラクトであって、前記TCRβまたはδ鎖が、配列番号7、19、および31から選択されるアミノ酸配列と少なくとも50%の配列同一性を有するCDR1;および/または配列番号8、20、および32から選択されるアミノ酸配列と少なくとも50%の配列同一性を有するCDR2をさらに含んでなる、抗原認識コンストラクト。
- 請求項1〜6のいずれか一項に記載の抗原認識コンストラクトであって、配列番号4、10、16、22、28、および34から選択されるアミノ酸配列と少なくとも50%の配列同一性を有するTCR可変鎖領域を含んでなる、抗原認識コンストラクト。
- 請求項1〜7のいずれか一項に記載の抗原認識コンストラクトであって、TCR結合断片を含んでなり、前記結合断片が、任意選択的に、配列番号1、2、3、または7、8、9または13、14、15、または19、20、21、または25、26、27または31、32、33のアミノ酸配列を有するCDR1〜CDR3配列から選択されるCDR1〜CDR3を含んでなる、抗原認識コンストラクト。
- 請求項1〜8のいずれか一項に記載の抗原認識コンストラクトをコードする核酸、または前記核酸を含んでなるベクター。
- 請求項1〜8のいずれか一項に記載の抗原認識コンストラクト、または請求項9に記載の核酸もしくはベクター、好ましくはリンパ球、好ましくはTリンパ球もしくはリンパ球前駆体、より好ましくはCD4もしくはCD8陽性T細胞、なおもより好ましくはγ/δT細胞であるT細胞を含んでなる、宿主細胞。
- 請求項1〜8のいずれか一項に記載の抗原認識コンストラクト、または請求項9に記載の核酸もしくはベクター、または請求項10に記載の宿主細胞、および薬学的に許容可能な担体、安定剤および/または賦形剤を含んでなる、医薬組成物。
- 医療で使用するための、好ましくは増殖性疾患、特にがんの診断、予防、および/または治療で使用するための、請求項1〜8のいずれか一項に記載の抗原認識コンストラクト、または請求項9に記載の核酸、または請求項10に記載のベクター、または請求項11に記載の宿主細胞、または請求項12に記載の医薬品組成物であって、前記がんが、好ましくは、非小細胞肺がん、小細胞肺がん、腎細胞、脳がん、胃がん、結腸直腸がん、肝細胞がん、頭頸部がん、膵臓がん、前立腺がん、白血病、乳がん、メルケル細胞がん、黒色腫、卵巣がん、膀胱がん、子宮がん、胆嚢および胆管がん、食道がん、またはそれらの組み合わせから選択される、医薬品組成物。
- a)前記生物学的サンプルを請求項3〜8のいずれか一項に記載のTCRに接触させるステップと、
b)前記生物学的サンプルへの前記TCRの結合を検出するステップと
を含んでなる、生物学的サンプル中のがんを検出する方法。 - 前記TCRが検出可能な標識を含んでなる、請求項13に記載の方法。
- 前記検出可能な標識が、放射性核種、フルオロフォア、およびビオチンからなる群から選択される、請求項14に記載の方法。
- 前記検出が、生体外、生体内または原位置で実施される、請求項13〜15のいずれかに記載の方法。
- 前記がんが、非小細胞肺がん、小細胞肺がん、腎細胞、脳がん、胃がん、結腸直腸がん、肝細胞がん、頭頸部がん、膵臓がん、前立腺がん、白血病、乳がん、メルケル細胞がん、黒色腫、卵巣がん、膀胱がん、子宮がん、胆嚢および胆管がん、食道がん、またはそれらの組み合わせである、請求項13〜16のいずれか一項に記載の方法
- 請求項3〜8のいずれか一項に記載のTCRである抗原認識コンストラクトであって、前記TCRが可溶性TCRである、抗原認識コンストラクト。
- 請求項3〜8のいずれか一項に記載のTCRである抗原認識コンストラクトであって、前記α鎖が配列番号4のアミノ酸配列と少なくとも95%同一であるTCRα可変ドメインを含んでなり、前記β鎖が配列番号10と少なくとも10%同一であるTCRβ可変ドメインを含んでなり、前記TCRがITAA−ペプチド−MHC分子複合体に特異的に結合する、抗原認識コンストラクト。
- 請求項3〜8のいずれか一項に記載のTCRであって、配列番号4に対して前記α鎖に少なくとも1つの変異を有し、および/または配列番号10に対して前記β鎖に少なくとも1つの変異を有し、前記TCRが、TAAペプチド−HLA分子複合体に対して、非変異TCRの少なくとも2倍の結合親和性および/または結合半減期を有する、TCR。
- 請求項3〜8に記載の抗原認識コンストラクトであって、配列番号4に対してα鎖中に少なくとも1つの変異を有し、および/または配列番号10に対してβ鎖中に少なくとも1つの変異を有し、前記TCRが非変異TCRと比較して修飾グリコシル化を有する、抗原認識コンストラクト。
- 配列番号4のα鎖CDR1、CDR2、およびCDR3からなる群から選択される少なくとも1つのα鎖相補性決定領域(CDR)および/または配列番号10のβ鎖CDR1、CDR2およびCDR3からなる群から選択される少なくとも1つのβ鎖相補性決定領域(CDR)を含んでなり、TAAペプチド−MHC分子複合体に特異的に結合する、TCR。
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KR20170032406A (ko) * | 2014-07-15 | 2017-03-22 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 치료를 위한 조작된 세포 |
CN105506065A (zh) * | 2014-09-25 | 2016-04-20 | 上海人类基因组研究中心 | 肝癌基因检测方法、检测试剂盒及其应用 |
GB201520583D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
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2016
- 2016-12-08 DE DE102016123859.7A patent/DE102016123859B3/de not_active Expired - Fee Related
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2017
- 2017-12-07 AU AU2017373815A patent/AU2017373815C1/en not_active Ceased
- 2017-12-07 CA CA3045234A patent/CA3045234A1/en not_active Abandoned
- 2017-12-07 JP JP2019528908A patent/JP2020511936A/ja active Pending
- 2017-12-07 US US15/835,095 patent/US10527623B2/en not_active Expired - Fee Related
- 2017-12-07 BR BR112019010699A patent/BR112019010699A2/pt not_active IP Right Cessation
- 2017-12-07 KR KR1020197019008A patent/KR20190086562A/ko active IP Right Grant
- 2017-12-07 WO PCT/EP2017/081893 patent/WO2018104478A1/en unknown
- 2017-12-07 MX MX2019006727A patent/MX2019006727A/es unknown
- 2017-12-07 CR CR20190276A patent/CR20190276A/es unknown
- 2017-12-07 PE PE2019001096A patent/PE20191081A1/es unknown
- 2017-12-07 EP EP17825768.9A patent/EP3551654A1/en not_active Withdrawn
- 2017-12-07 CN CN201780075298.4A patent/CN110036027A/zh active Pending
- 2017-12-08 TW TW106143135A patent/TW201828977A/zh unknown
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2018
- 2018-07-02 US US16/025,434 patent/US10725044B2/en not_active Expired - Fee Related
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2020
- 2020-03-24 US US16/828,577 patent/US20200249233A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2016156202A1 (en) * | 2015-03-27 | 2016-10-06 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various tumors |
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AU2017373815A1 (en) | 2019-06-27 |
DE102016123859B3 (de) | 2018-03-01 |
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US10527623B2 (en) | 2020-01-07 |
BR112019010699A2 (pt) | 2019-10-22 |
US10725044B2 (en) | 2020-07-28 |
EP3551654A1 (en) | 2019-10-16 |
CA3045234A1 (en) | 2018-06-14 |
WO2018104478A1 (en) | 2018-06-14 |
AU2017373815C1 (en) | 2021-08-26 |
CN110036027A (zh) | 2019-07-19 |
US20180306789A1 (en) | 2018-10-25 |
US20200249233A1 (en) | 2020-08-06 |
PE20191081A1 (es) | 2019-08-20 |
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