JPWO2021091359A5

JPWO2021091359A5 -

Info

Publication number: JPWO2021091359A5
Application number: JP2022525129A
Authority: JP
Publication date: 2023-11-16

Description

産業上の利用可能性
本発明によるＬｒｉｇ－１タンパク質のエピトープに特異的に結合する抗体または抗原結合断片は、制御性Ｔ細胞上に存在する本発明のエピトープに特異的に結合して前記制御性Ｔ細胞の機能を抑制し、エフェクターＴ細胞の活性は維持あるいは上昇させて、癌の予防、改善または治療に非常に効率的に使用することができる。
本願発明の例示的な態様を以下に記載する。
＜１＞Ｌｒｉｇ－１（ｌｅｕｃｉｎｅ－ｒｉｃｈａｎｄｉｍｍｕｎｏｇｌｏｂｕｌｉｎ－ｌｉｋｅｄｏｍａｉｎｓ１）タンパク質のエピトープであって、
配列番号７～配列番号７０で表されるアミノ酸配列からなるポリペプチドから構成された群より選択される少なくともいずれか１つのポリペプチドを含むエピトープ。
＜２＞Ｌｒｉｇ－１（ｌｅｕｃｉｎｅ－ｒｉｃｈａｎｄｉｍｍｕｎｏｇｌｏｂｕｌｉｎ－ｌｉｋｅｄｏｍａｉｎｓ１）タンパク質のエピトープであって、
配列番号７１または配列番号７２で表されるアミノ酸配列からなるポリペプチドを含むエピトープ。
＜３＞配列番号７～配列番号７０で表されるアミノ酸配列からなるポリペプチドから構成された群より選択される少なくともいずれか１つのポリペプチドを含むエピトープに特異的に結合する抗体または抗原結合断片。
＜４＞配列番号７１または配列番号７２で表されるアミノ酸配列からなるポリペプチドを含むエピトープに特異的に結合する抗体または抗原結合断片。
＜５＞＜１＞または＜２＞のエピトープをコーディングする核酸分子。
＜６＞＜５＞の核酸分子が挿入された発現ベクター。
＜７＞＜６＞の発現ベクターが形質感染した宿主細胞株。
＜８＞＜３＞または＜４＞の抗体または抗原結合断片を有効成分として含む癌の予防または治療用薬学組成物。
＜９＞前記癌は、胃癌、肝臓癌、膠細胞腫、卵巣癌、大膓癌、頭頸部癌、膀胱癌、腎細胞癌、乳癌、転移癌、前立腺癌、膵臓癌、黒色腫または肺癌である、＜８＞の薬学組成物。
＜１０＞＜３＞または＜４＞の抗体または抗原結合断片；および薬物を含む抗体－薬物結合体。
＜１１＞配列番号７～配列番号７０で表されるアミノ酸配列からなるポリペプチドから構成された群より選択される少なくともいずれか１つのポリペプチドを含むエピトープに特異的に結合する抗体または抗原結合断片を薬学的有効量で個体に投与するステップを含む癌の予防または治療方法。
＜１２＞配列番号７１または配列番号７２で表されるアミノ酸配列からなるポリペプチドを含むエピトープに特異的に結合する抗体または抗原結合断片を薬学的有効量で個体に投与するステップを含む癌の予防または治療方法。 Industrial Applicability The antibody or antigen-binding fragment of the present invention that specifically binds to the epitope of the Lrig-1 protein binds specifically to the epitope of the present invention present on regulatory T cells, and By suppressing T cell function and maintaining or increasing effector T cell activity, it can be used very efficiently for the prevention, improvement, or treatment of cancer.
Exemplary embodiments of the present invention are described below.
<1> An epitope of Lrig-1 (leucine-rich and immunoglobulin-like domains 1) protein,
An epitope comprising at least one polypeptide selected from the group consisting of polypeptides consisting of the amino acid sequences represented by SEQ ID NO: 7 to SEQ ID NO: 70.
<2> An epitope of Lrig-1 (leucine-rich and immunoglobulin-like domains 1) protein,
An epitope comprising a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 71 or SEQ ID NO: 72.
<3> An antibody or antigen-binding fragment that specifically binds to an epitope containing at least one polypeptide selected from the group consisting of polypeptides consisting of the amino acid sequences represented by SEQ ID NO: 7 to SEQ ID NO: 70. .
<4> An antibody or antigen-binding fragment that specifically binds to an epitope containing a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 71 or SEQ ID NO: 72.
<5> A nucleic acid molecule encoding the epitope of <1> or <2>.
<6> An expression vector into which the nucleic acid molecule of <5> has been inserted.
<7> A host cell line transfected with the expression vector of <6>.
<8> A pharmaceutical composition for preventing or treating cancer, comprising the antibody or antigen-binding fragment of <3> or <4> as an active ingredient.
<9> The cancer is gastric cancer, liver cancer, glioma, ovarian cancer, Otae cancer, head and neck cancer, bladder cancer, renal cell cancer, breast cancer, metastatic cancer, prostate cancer, pancreatic cancer, melanoma, or lung cancer. The pharmaceutical composition of <8>.
<10> The antibody or antigen-binding fragment of <3> or <4>; and an antibody-drug conjugate comprising a drug.
<11> An antibody or antigen-binding fragment that specifically binds to an epitope containing at least one polypeptide selected from the group consisting of polypeptides consisting of the amino acid sequences represented by SEQ ID NO: 7 to SEQ ID NO: 70. A method for preventing or treating cancer, comprising administering to an individual a pharmaceutically effective amount of.
<12> Cancer prevention comprising administering to an individual a pharmaceutically effective amount of an antibody or antigen-binding fragment that specifically binds to an epitope containing a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 71 or SEQ ID NO: 72. or treatment methods.

Claims

An epitope of Lrig-1 (leucine-rich and immunoglobulin-like domains 1) protein,
An epitope comprising at least one polypeptide selected from the group consisting of polypeptides consisting of the amino acid sequences represented by SEQ ID NO: 7 to SEQ ID NO: 70.

An epitope of Lrig-1 (leucine-rich and immunoglobulin-like domains 1) protein,
An epitope comprising a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 71 or SEQ ID NO: 72.

An antibody or antigen-binding fragment that specifically binds to an epitope containing at least one polypeptide selected from the group consisting of polypeptides consisting of the amino acid sequences represented by SEQ ID NO: 7 to SEQ ID NO: 70.

An antibody or antigen-binding fragment that specifically binds to an epitope comprising a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 71 or SEQ ID NO: 72.

A nucleic acid molecule encoding an epitope according to claim 1 or 2.

An expression vector into which the nucleic acid molecule according to claim 5 has been inserted.

A host cell line transformed with the expression vector according to claim 6.

A pharmaceutical composition for preventing or treating cancer, comprising the antibody or antigen-binding fragment according to claim 3 or 4 as an active ingredient.

The cancer is gastric cancer, liver cancer, glioma, ovarian cancer, Otae cancer, head and neck cancer, bladder cancer, renal cell cancer, breast cancer, metastatic cancer, prostate cancer, pancreatic cancer, melanoma, or lung cancer. The pharmaceutical composition according to item 8.

An antibody-drug conjugate comprising the antibody or antigen-binding fragment according to claim 3 or 4; and a drug.