JPWO2021191607A5 - - Google Patents
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- JPWO2021191607A5 JPWO2021191607A5 JP2022557873A JP2022557873A JPWO2021191607A5 JP WO2021191607 A5 JPWO2021191607 A5 JP WO2021191607A5 JP 2022557873 A JP2022557873 A JP 2022557873A JP 2022557873 A JP2022557873 A JP 2022557873A JP WO2021191607 A5 JPWO2021191607 A5 JP WO2021191607A5
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- antibody
- cells
- antibody conjugate
- cell lymphoma
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- 229940127121 immunoconjugate Drugs 0.000 claims description 39
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 26
- 230000003211 malignant effect Effects 0.000 claims description 19
- 101000662909 Homo sapiens T cell receptor beta constant 1 Proteins 0.000 claims description 14
- 101000662902 Homo sapiens T cell receptor beta constant 2 Proteins 0.000 claims description 14
- 102100037272 T cell receptor beta constant 1 Human genes 0.000 claims description 14
- 102100037298 T cell receptor beta constant 2 Human genes 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 230000035772 mutation Effects 0.000 claims description 12
- 102220490832 Mannosyl-oligosaccharide glucosidase_Y32F_mutation Human genes 0.000 claims description 10
- 208000000389 T-cell leukemia Diseases 0.000 claims description 10
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims description 10
- 206010042971 T-cell lymphoma Diseases 0.000 claims description 10
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 10
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 claims description 4
- 208000002460 Enteropathy-Associated T-Cell Lymphoma Diseases 0.000 claims description 4
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 claims description 4
- 229940122429 Tubulin inhibitor Drugs 0.000 claims description 4
- 206010002449 angioimmunoblastic T-cell lymphoma Diseases 0.000 claims description 4
- 210000004027 cell Anatomy 0.000 claims description 4
- 230000000973 chemotherapeutic effect Effects 0.000 claims description 4
- 206010066957 hepatosplenic T-cell lymphoma Diseases 0.000 claims description 4
- BSDCIRGNJKZPFV-GWOFURMSSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1Cl BSDCIRGNJKZPFV-GWOFURMSSA-N 0.000 claims description 2
- 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 claims description 2
- 101000763322 Homo sapiens M1-specific T cell receptor beta chain Proteins 0.000 claims description 2
- 101000763321 Homo sapiens T cell receptor beta chain MC.7.G5 Proteins 0.000 claims description 2
- 102100026964 M1-specific T cell receptor beta chain Human genes 0.000 claims description 2
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 claims description 2
- 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 claims description 2
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 2
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 claims description 2
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 claims description 2
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical group CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000010494 dissociation reaction Methods 0.000 claims description 2
- 230000005593 dissociations Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
- 201000005962 mycosis fungoides Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000000814 primary cutaneous anaplastic large cell lymphoma Diseases 0.000 claims description 2
- 102220085627 rs762346893 Human genes 0.000 claims description 2
- 230000008685 targeting Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 8
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000036210 malignancy Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
Description
上記の明細書で言及されたすべての刊行物は、参照により本明細書に組み入れられる。本発明の記載された方法および系の様々な改変および変形が、本発明の範囲および精神から逸脱することなく、当業者には明らかであろう。本発明は特定の好ましい態様に関連して説明されてきたが、権利が請求されている発明はそのような特定の態様に不当に限定されるべきではないことが理解されるべきである。実際に、分子生物学または関連分野の当業者に明らかである、本発明を実施するための記載された形態の様々な改変は、以下の特許請求の範囲内に属することが意図される。
本発明は、例えば、以下の項目を提供する。
（項目１）
ＴＣＲβ鎖定常領域（ＴＲＢＣ）に特異的に結合する抗体コンジュゲートであって、前記抗体は０．００１秒
－１
～０．３秒
－１
の範囲の解離速度定数（ｋ
ｄ
）を有する、抗体コンジュゲート。
（項目２）
前記抗体が、０．００２秒
－１
～０．１秒
－１
の範囲のｋ
ｄ
を有する、項目１に記載の抗体コンジュゲート。
（項目３）
前記抗体が、化学療法実体、放射性核種または検出実体にコンジュゲートされる、項目１または２のいずれかに記載の抗体コンジュゲート。
（項目４）
前記化学療法実体がチューブリン阻害剤である、項目３に記載の抗体コンジュゲート。
（項目５）
前記チューブリン阻害剤がＭＭＡＥである、項目４に記載の抗体コンジュゲート。
（項目６）
前記抗体コンジュゲートが、配列番号１に示される配列を有するＶＨドメインと配列番号２に示される配列を有するＶＬドメインとを有する参照抗体の内部移行と比較して、標的細胞への結合の際に増大した内部移行を有する、項目１～５のいずれかに記載の抗体コンジュゲート。
（項目７）
前記抗体がＴＲＢＣ１に特異的に結合する、項目１～６のいずれかに記載の抗体コンジュゲート。
（項目８）
前記抗体が、配列番号１に示される配列を有するＶＨドメインと配列番号２に示される配列を有するＶＬドメインとを有する参照抗体と比較して、以下の変異または変異の組み合わせ：
－前記ＶＨドメイン中のＧ１０６Ａ；
－前記ＶＨドメイン中のＹ３２Ｆ；
－前記ＶＨドメイン中のＧ３１Ｓ；
－前記ＶＨドメイン中のＧ２６ＰおよびＴ２８Ｋ；または
－前記ＶＨドメイン中のＹ１０２Ｍ
の１つを含む、項目７に記載の抗体コンジュゲート。
（項目９）
前記抗体が、配列番号１に示される配列を有するＶＨドメインと配列番号２に示される配列を有するＶＬドメインとを有する参照抗体と比較して、以下の変異：
－前記ＶＨドメイン中のＧ１０６Ａ
を含む、項目８に記載の抗体コンジュゲート。
（項目１０）
前記抗体がＴＲＢＣ２に特異的に結合する、項目１～６のいずれかに記載の抗体コンジュゲート。
（項目１１）
前記抗体が、配列番号１に示される配列を有するＶＨドメインと配列番号２に示される配列を有するＶＬドメインとを有する参照抗体と比較して、以下の変異または変異の組み合わせ：
－前記ＶＨドメイン中のＴ２８Ｋ、Ｙ３２Ｆ、Ａ１００Ｎ、Ｙ１０２ＬおよびＮ１０３Ｍ、ならびに前記ＶＬドメイン中のＮ３５Ｒ；
－前記ＶＨドメイン中のＴ２８Ｋ、Ｙ３２ＦおよびＡ１００Ｎ；または
－前記ＶＨドメイン中のＴ２８Ｒ、Ｙ３２ＦおよびＡ１００Ｎ
の１つを含む、項目１０に記載の抗体コンジュゲート。
（項目１２）
前記抗体が、配列番号１に示される配列を有するＶＨドメインと配列番号２に示される配列を有するＶＬドメインとを有する参照抗体と比較して、以下の変異の組み合わせ：
－前記ＶＨドメイン中のＴ２８Ｋ、Ｙ３２Ｆ、Ａ１００ＮおよびＮ１０３Ｌ、ならびに前記ＶＬドメイン中のＮ３５Ｒ
の１つを含む、項目１１に記載の抗体コンジュゲート。
（項目１３）
Ｔ細胞リンパ腫または白血病の処置において使用するための、項目１～１２のいずれか一項に記載の抗体コンジュゲート。
（項目１４）
対象におけるＴ細胞リンパ腫または白血病の前記処置が、悪性Ｔ細胞と同じＴＲＢＣを発現する正常Ｔ細胞と一緒に、前記悪性Ｔ細胞の選択的枯渇を引き起こすが、前記悪性Ｔ細胞によって発現されないＴＲＢＣを発現する正常Ｔ細胞の枯渇を引き起こさないようにするために、前記対象に前記抗体コンジュゲートを投与する工程を含む、項目１３に記載の使用のための抗体コンジュゲート。
（項目１５）
前記方法が、前記対象由来の悪性Ｔ細胞がＴＲＢＣ１またはＴＲＢＣ２を発現するかどうかを決定するために、前記対象由来の悪性Ｔ細胞の前記ＴＣＲβ鎖定常領域（ＴＣＲＢ）を調べる工程をさらに含む、項目１４に記載の使用のための抗体コンジュゲート。
（項目１６）
前記Ｔ細胞リンパ腫または白血病が、末梢性Ｔ細胞リンパ腫、非特定型（ＰＴＣＬ－ＮＯＳ）；血管免疫芽球性Ｔ細胞リンパ腫（ＡＩＴＬ）、未分化大細胞型リンパ腫（ＡＬＣＬ）、腸症関連Ｔ細胞リンパ腫（ＥＡＴＬ）、肝脾Ｔ細胞リンパ腫（ＨＳＴＬ）、節外性ＮＫ／Ｔ細胞リンパ腫鼻型、皮膚Ｔ細胞リンパ腫、原発性皮膚ＡＬＣＬ、Ｔ細胞性前リンパ球性白血病およびＴ細胞急性リンパ芽球性白血病から選択される、項目１３～１５のいずれかに記載の使用のための抗体コンジュゲート。
（項目１７）
対象中のＴＲＢＣを発現する細胞への化学療法薬の送達を標的とするための方法における使用のための、項目３～１２のいずれかに記載の抗体コンジュゲート。
（項目１８）
項目１～１２のいずれかに記載の抗体コンジュゲートと、薬学的に許容され得るキャリア、希釈剤、賦形剤または補助剤とを含む薬学的組成物。
（項目１９）
Ｔ細胞リンパ腫または白血病に罹患している対象を処置するための適切な療法を選択するための方法であって、
ｉ）前記対象から単離された試料中の悪性Ｔ細胞がＴＲＢＣ１またはＴＲＢＣ２を発現するかどうかを決定することと；
ｉｉ）前記悪性Ｔ細胞の前記ＴＲＢＣ１またはＴＲＢＣ２発現に基づいて、項目１３～１６のいずれかに記載の使用のための抗体コンジュゲートを選択することと；
を含む、方法。
（項目２０）
項目１３～１６のいずれかに記載の使用のための抗体コンジュゲートを含む療法を受けるために、Ｔ細胞リンパ腫または白血病に罹患している対象を選択するための方法であって、
ｉ）前記対象から単離された試料中の悪性Ｔ細胞がＴＲＢＣ１またはＴＲＢＣ２を発現するかどうかを決定することと；
ｉｉ）前記悪性Ｔ細胞の前記ＴＲＢＣ１またはＴＲＢＣ２発現に基づいて、項目１３～１６のいずれかに記載の使用のための抗体コンジュゲートに基づく療法を受けるために前記対象を選択することと；
を含む、方法。
All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described methods and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with certain preferred embodiments, it should be understood that the claimed invention should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims.
The present invention provides, for example, the following items.
(Item 1)
An antibody conjugate that specifically binds to the TCR β chain constant region (TRBC), wherein said antibody has a dissociation rate constant (k d ) in the range of 0.001 s -1 to 0.3 s -1 . Conjugate.
(Item 2)
The antibody conjugate of item 1, wherein said antibody has a k d in the range of 0.002 s -1 to 0.1 s -1 .
(Item 3)
Antibody conjugate according to any of items 1 or 2, wherein said antibody is conjugated to a chemotherapeutic entity, a radionuclide or a detection entity.
(Item 4)
Antibody conjugate according to item 3, wherein said chemotherapeutic entity is a tubulin inhibitor.
(Item 5)
The antibody conjugate according to item 4, wherein the tubulin inhibitor is MMAE.
(Item 6)
When the antibody conjugate binds to a target cell, the internalization of a reference antibody having a VH domain having the sequence set forth in SEQ ID NO:1 and a VL domain having the sequence set forth in SEQ ID NO:2 increases. Antibody conjugate according to any of items 1 to 5, having increased internalization.
(Item 7)
The antibody conjugate according to any of items 1 to 6, wherein the antibody specifically binds to TRBC1.
(Item 8)
The following mutations or combinations of mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- G106A in said VH domain;
- Y32F in said VH domain;
- G31S in said VH domain;
- G26P and T28K in said VH domain; or
- Y102M in the VH domain
The antibody conjugate according to item 7, comprising one of the following.
(Item 9)
The following mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- G106A in the VH domain
The antibody conjugate according to item 8, comprising:
(Item 10)
The antibody conjugate according to any of items 1 to 6, wherein the antibody specifically binds to TRBC2.
(Item 11)
The following mutations or combinations of mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- T28K, Y32F, A100N, Y102L and N103M in said VH domain and N35R in said VL domain;
- T28K, Y32F and A100N in said VH domain; or
- T28R, Y32F and A100N in the VH domain
The antibody conjugate according to item 10, comprising one of the following.
(Item 12)
The following combination of mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- T28K, Y32F, A100N and N103L in said VH domain and N35R in said VL domain
The antibody conjugate according to item 11, comprising one of the following.
(Item 13)
Antibody conjugate according to any one of items 1 to 12 for use in the treatment of T-cell lymphoma or leukemia.
(Item 14)
said treatment of T-cell lymphoma or leukemia in a subject causes selective depletion of said malignant T cells, with normal T cells expressing the same TRBCs as malignant T cells, but expressing TRBCs not expressed by said malignant T cells. 14. An antibody conjugate for use according to item 13, comprising administering said antibody conjugate to said subject to avoid causing depletion of normal T cells.
(Item 15)
The method further comprises the step of examining the TCR β chain constant region (TCRB) of malignant T cells from the subject to determine whether the malignant T cells from the subject express TRBC1 or TRBC2. Antibody conjugate for use according to 14.
(Item 16)
The T-cell lymphoma or leukemia is peripheral T-cell lymphoma, non-specific (PTCL-NOS); angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), enteropathy-associated T-cell lymphoma (EATL), hepatosplenic T-cell lymphoma (HSTL), extranodal NK/T-cell lymphoma nasal type, cutaneous T-cell lymphoma, primary cutaneous ALCL, T-cell prolymphocytic leukemia and T-cell acute lymphoblastoid Antibody conjugate for use according to any of items 13 to 15, selected from leukemia.
(Item 17)
An antibody conjugate according to any of items 3 to 12 for use in a method for targeting the delivery of a chemotherapeutic agent to cells expressing TRBC in a subject.
(Item 18)
A pharmaceutical composition comprising an antibody conjugate according to any of items 1 to 12 and a pharmaceutically acceptable carrier, diluent, excipient or adjuvant.
(Item 19)
A method for selecting an appropriate therapy for treating a subject suffering from T-cell lymphoma or leukemia, the method comprising:
i) determining whether malignant T cells in a sample isolated from said subject express TRBC1 or TRBC2;
ii) selecting an antibody conjugate for use according to any of items 13-16 based on said TRBC1 or TRBC2 expression of said malignant T cells;
including methods.
(Item 20)
17. A method for selecting a subject suffering from T-cell lymphoma or leukemia to receive therapy comprising an antibody conjugate for use according to any of items 13-16, comprising:
i) determining whether malignant T cells in a sample isolated from said subject express TRBC1 or TRBC2;
ii) selecting said subject to receive an antibody conjugate-based therapy for use according to any of items 13 to 16 based on said TRBC1 or TRBC2 expression of said malignant T cells;
including methods.
Claims (20)
－前記ＶＨドメイン中のＧ１０６Ａ；
－前記ＶＨドメイン中のＹ３２Ｆ；
－前記ＶＨドメイン中のＧ３１Ｓ；
－前記ＶＨドメイン中のＧ２６ＰおよびＴ２８Ｋ；または
－前記ＶＨドメイン中のＹ１０２Ｍ
の１つを含む、請求項７に記載の抗体コンジュゲート。 The following mutations or combinations of mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- G106A in said VH domain;
- Y32F in said VH domain;
- G31S in said VH domain;
- G26P and T28K in said VH domain; or - Y102M in said VH domain.
8. The antibody conjugate of claim 7, comprising one of:
－前記ＶＨドメイン中のＧ１０６Ａ
を含む、請求項８に記載の抗体コンジュゲート。 The following mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- G106A in the VH domain
9. The antibody conjugate of claim 8, comprising:
－前記ＶＨドメイン中のＴ２８Ｋ、Ｙ３２Ｆ、Ａ１００Ｎ、Ｙ１０２ＬおよびＮ１０３Ｍ、ならびに前記ＶＬドメイン中のＮ３５Ｒ；
－前記ＶＨドメイン中のＴ２８Ｋ、Ｙ３２ＦおよびＡ１００Ｎ；または
－前記ＶＨドメイン中のＴ２８Ｒ、Ｙ３２ＦおよびＡ１００Ｎ
の１つを含む、請求項１０に記載の抗体コンジュゲート。 The following mutations or combinations of mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- T28K, Y32F, A100N, Y102L and N103M in said VH domain and N35R in said VL domain;
- T28K, Y32F and A100N in said VH domain; or - T28R, Y32F and A100N in said VH domain.
11. The antibody conjugate of claim 10, comprising one of:
－前記ＶＨドメイン中のＴ２８Ｋ、Ｙ３２Ｆ、Ａ１００ＮおよびＮ１０３Ｌ、ならびに前記ＶＬドメイン中のＮ３５Ｒ
の１つを含む、請求項１１に記載の抗体コンジュゲート。 The following combination of mutations compared to a reference antibody in which the antibody has a VH domain having the sequence shown in SEQ ID NO: 1 and a VL domain having the sequence shown in SEQ ID NO: 2:
- T28K, Y32F, A100N and N103L in said VH domain and N35R in said VL domain
12. The antibody conjugate of claim 11, comprising one of:
前記試料中の前記悪性Ｔ細胞がＴＲＢＣ１またはＴＲＢＣ２を発現するかどうかを決定すること
を含み、前記悪性Ｔ細胞の前記ＴＲＢＣ１またはＴＲＢＣ２発現が、請求項１３～１６のいずれかに記載の組成物の選択を示す、方法。 A method of determining TRBC1 or TRBC2 expression on malignant T cells in a sample isolated from a subject as an indicator for selecting an appropriate therapy for treating a subject suffering from T-cell lymphoma or leukemia. Therefore, the method is
determining whether the malignant T cells in the sample express TRBC1 or TRBC2;
wherein said TRBC1 or TRBC2 expression of said malignant T cells is indicative of selection of the composition of any of claims 13-16.
前記対象から単離された前記試料中の前記悪性Ｔ細胞がＴＲＢＣ１またはＴＲＢＣ２を発現するかどうかを決定すること
を含み、前記悪性Ｔ細胞の前記ＴＲＢＣ１またはＴＲＢＣ２発現が、前記対象の選択を示す、方法。
malignancy in a sample isolated from said subject as an indicator for selecting a subject suffering from T-cell lymphoma or leukemia to undergo therapy comprising a composition according to any of claims 13 to 16. A method for determining TRBC1 or TRBC2 expression in T cells , the method comprising:
determining whether the malignant T cells in the sample isolated from the subject express TRBC1 or TRBC2.
wherein said TRBC1 or TRBC2 expression on said malignant T cell is indicative of selection of said subject.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB2004263.6A GB202004263D0 (en) | 2020-03-24 | 2020-03-24 | Antibody conjugate |
| GB2004263.6 | 2020-03-24 | ||
| PCT/GB2021/050719 WO2021191607A1 (en) | 2020-03-24 | 2021-03-24 | Trbc beta antibody conjugate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2023518566A JP2023518566A (en) | 2023-05-02 |
| JPWO2021191607A5 true JPWO2021191607A5 (en) | 2024-01-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022557873A Pending JP2023518566A (en) | 2020-03-24 | 2021-03-24 | TRBCβ antibody conjugate |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20230109275A1 (en) |
| EP (1) | EP4126948A1 (en) |
| JP (1) | JP2023518566A (en) |
| CN (1) | CN115667306A (en) |
| GB (1) | GB202004263D0 (en) |
| WO (1) | WO2021191607A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11885807B2 (en) | 2014-03-05 | 2024-01-30 | Autolus Limited | Method for depleting malignant T-cells |
| WO2023215560A1 (en) | 2022-05-05 | 2023-11-09 | Atoosa Corporation | Tumor cell/immune cell multivalent receptor engager – bio-nanoparticle (timre-bnp) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1171596A1 (en) | 1999-04-16 | 2002-01-16 | Celltech Therapeutics Limited | Synthetic transmembrane components |
| SG11201606583VA (en) | 2014-03-05 | 2016-09-29 | Ucl Business Plc | Chimeric antigen receptor (car) with antigen binding domains to the t cell receptor beta constant region |
| BR112016022910A2 (en) | 2014-04-11 | 2017-10-17 | Medimmune Llc | bispecific her2 antibodies |
| WO2015155345A1 (en) | 2014-04-11 | 2015-10-15 | Medimmune Limited | Antibodies and antibody-drug conjugates |
| GB201504840D0 (en) | 2015-03-23 | 2015-05-06 | Ucl Business Plc | Chimeric antigen receptor |
| GB201709203D0 (en) * | 2017-06-09 | 2017-07-26 | Autolus Ltd | Antigen-binding domain |
-
2020
- 2020-03-24 GB GBGB2004263.6A patent/GB202004263D0/en not_active Ceased
-
2021
- 2021-03-24 JP JP2022557873A patent/JP2023518566A/en active Pending
- 2021-03-24 EP EP21716524.0A patent/EP4126948A1/en active Pending
- 2021-03-24 CN CN202180035971.8A patent/CN115667306A/en active Pending
- 2021-03-24 WO PCT/GB2021/050719 patent/WO2021191607A1/en unknown
- 2021-03-24 US US17/913,649 patent/US20230109275A1/en active Pending
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