JP2020099326A5 - - Google Patents

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JP2020099326A5
JP2020099326A5 JP2019238469A JP2019238469A JP2020099326A5 JP 2020099326 A5 JP2020099326 A5 JP 2020099326A5 JP 2019238469 A JP2019238469 A JP 2019238469A JP 2019238469 A JP2019238469 A JP 2019238469A JP 2020099326 A5 JP2020099326 A5 JP 2020099326A5
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cancer
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composition
composition according
egfr
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JP2020099326A (en
JP7088902B2 (en
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ヒトリンパ球を含む組成物であって、該ヒトリンパ球が、ヒトリンパ球の表面にキメラ抗原受容体タンパク質を含み、ここでキメラ抗原受容体タンパク質が、ヒト上皮成長因子受容体（EGFR）の２８７〜３０２番目のアミノ酸エピトープに結合する細胞外結合領域を含む、前記組成物。 A composition comprising human lymphocytes, wherein the human lymphocyte comprises a chimeric antigen receptor protein on the surface of the human lymphocyte, wherein the chimeric antigen receptor protein is 287-302 of the human epidermal growth factor receptor (EGFR). The composition comprising an extracellular binding region that binds to a second amino acid epitope. キメラ抗原受容体タンパク質が、膜貫通領域および細胞内シグナル領域をさらに含む、請求項１に記載の組成物。 The composition of claim 1, wherein the chimeric antigen receptor protein further comprises a transmembrane region and an intracellular signaling region. 細胞外結合領域、膜貫通領域および細胞内シグナル領域が、順に連結されている、請求項２に記載の組成物。 The composition according to claim 2, wherein the extracellular binding region, the transmembrane region, and the intracellular signal region are sequentially linked. 膜貫通領域が、CD8またはCD28の膜貫通領域およびヒンジ領域の配列を含む、請求項２または３に記載の組成物。 The composition of claim 2 or 3, wherein the transmembrane region comprises an arrangement of a transmembrane region and a hinge region of CD8 or CD28. 細胞内シグナル領域が、CD3ζ、FcεRIγ、CD28、CD137、CD134の細胞内シグナル領域の配列、およびこれらの組み合わせから選ばれる、請求項２〜４のいずれか一項に記載の組成物。 The composition according to any one of claims 2 to 4, wherein the intracellular signal region is selected from the sequence of the intracellular signal region of CD3ζ, FcεRIγ, CD28, CD137, CD134, and a combination thereof. キメラ抗原受容体タンパク質が、配列番号３１〜３４のいずれか１つの配列に対して少なくとも９５％の配列相同性を有する、請求項１〜５のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 5, wherein the chimeric antigen receptor protein has at least 95% sequence homology to any one of the sequences of SEQ ID NOs: 31 to 34. 細胞外結合領域が、配列番号３１〜３４のいずれかのアミノ酸１〜２４０に対して少なくとも９５％の配列相同性を有する一本鎖抗体scFvを含む、請求項１〜５のいずれか一項に記載の組成物。 In any one of claims 1-5, the extracellular binding region comprises a single chain antibody scFv having at least 95% sequence homology to amino acids 1-240 of any of SEQ ID NOs: 31-34. The composition described. キメラ抗原受容体タンパク質が、
scFv(EGFR)-CD8-CD3ζ、
scFv(EGFR)-CD8-CD137-CD3ζ、
scFv(EGFR)-CD28-CD28-CD3ζ、
scFv(EGFR)-CD28-CD28-CD137-CD3ζ
または、これらの組み合わせのいずれか１つであり、ここで、前記キメラ抗原受容体タンパク質における1番目のCD28はその膜貫通領域を、2番目のCD28はその細胞内シグナル領域を表す、請求項１〜７のいずれか一項に記載の組成物。 Chimeric antigen receptor protein
scFv (EGFR) -CD8-CD3ζ,
scFv (EGFR) -CD8-CD137-CD3ζ,
scFv (EGFR) -CD28-CD28-CD3ζ,
scFv (EGFR) -CD28-CD28-CD137-CD3ζ
Alternatively, it is any one of these combinations, wherein the first CD28 in the chimeric antigen receptor protein represents its transmembrane region and the second CD28 represents its intracellular signal region. The composition according to any one of 7 to 7. 組成物が、癌の処置に用いるためである、請求項１〜８のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 8, for which the composition is used for treating cancer. 処置が、EGFRvIIIの発現またはEGFRの高度発現を伴う上皮由来の癌性腫瘍の処置を含む、請求項９に記載の組成物。 The composition of claim 9, wherein the treatment comprises treating an epithelial-derived cancerous tumor with expression of EGFRvIII or high expression of EGFR. 癌が、非小細胞肺癌、膀胱癌、卵巣癌、乳癌、頭頚部扁平上皮癌、膠細胞腫、膵臓腺癌、食道癌、胃癌、前立腺癌、結腸癌、またはこれらの組み合わせを含む、請求項９または１０に記載の組成物。 Claim that the cancer comprises non-small cell lung cancer, bladder cancer, ovarian cancer, breast cancer, squamous cell carcinoma of the head and neck, glial cell carcinoma, pancreatic adenocarcinoma, esophageal cancer, gastric cancer, prostate cancer, colon cancer, or a combination thereof. The composition according to 9 or 10. 癌が、膵臓腺癌である、請求項９〜１１のいずれか一項に記載の組成物。 The composition according to any one of claims 9 to 11, wherein the cancer is pancreatic adenocarcinoma.
JP2019238469A 2019-12-27 2019-12-27 Nucleic acid encoding the chimeric antigen receptor protein and T lymphocytes expressing the chimeric antigen receptor protein Active JP7088902B2 (en)

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JP2020099326A5 true JP2020099326A5 (en) 2020-12-17
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CN103596981B (en) * 2011-04-08 2017-06-16 美国卫生和人力服务部 Anti-epidermal growth factor receptor variant III Chimeric antigen receptors and its purposes for treating cancer
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