JP7236216B2 - がんのネオエピトープ - Google Patents
がんのネオエピトープ Download PDFInfo
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- JP7236216B2 JP7236216B2 JP2017555492A JP2017555492A JP7236216B2 JP 7236216 B2 JP7236216 B2 JP 7236216B2 JP 2017555492 A JP2017555492 A JP 2017555492A JP 2017555492 A JP2017555492 A JP 2017555492A JP 7236216 B2 JP7236216 B2 JP 7236216B2
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Description
>254 NM_001000.3 RPL39 Missense p.M29K A->T Normal: WIRMKTGNK, AF: 0.179104477612 TPM: 1023.96 TPM_MEDIAN: 7.35 LL: 183.395820896 netMHC: 242.96 Allele: HLA-A0301 WIRKKTGNK
であってよい。
Claims (6)
- がん免疫療法のための薬剤を生成する方法であって、
少なくとも1つの患者特異的及びがん特異的ながんネオエピトープを含有するアミノ酸の長さが7~11である複数のペプチドをインシリコで生成するために患者の組織由来の腫瘍試料のオミクスデータをその患者の同じ組織由来の正常試料のオミクスデータと比較するステップであって、前記腫瘍試料及び前記正常試料のそれぞれからのオミクスデータには、全ゲノム配列決定データ、エクソーム配列決定データ、及び/又はトランスクリプトームデータからなる群から選択されるデータが含まれる、ステップと、
前記アミノ酸の長さが7~11である複数のペプチドをインシリコでフィルタリングし、そのようにしてネオエピトープ配列のサブセットを得るステップであって、前記フィルタリングは、突然変異の種類によるフィルタリング、発現の強さによるフィルタリング、細胞内の位置によるフィルタリング、及び患者のHLA型への結合親和性によるフィルタリングである、ステップと、
前記ネオエピトープ配列のサブセットからの配列情報を使用してアミノ酸の長さが7~11である少なくとも1つの合成ペプチドを調製するステップと、
組換え抗体を単離するためにアミノ酸の長さが7~11である前記合成ペプチドを使用するステップと、
前記組換え抗体の相補性決定領域の配列情報を得るステップと、
前記組換え抗体の相補性決定領域の配列情報を使用して合成抗体を生成するステップと、
前記合成抗体を治療剤又は診断薬に連結し、そのようにして薬剤を得るステップと
を含んでなる方法。 - 組換え抗体を単離するためにアミノ酸の長さが7~11である前記合成ペプチドを使用するステップは、ファージパニングを含んでなる、請求項1に記載の方法。
- 前記合成抗体は、ヒト抗体の足場上へのCDR又はSDRのグラフティングを使用して生成される、請求項1に記載の方法。
- 前記治療剤又は診断薬は、化学療法薬、放射性同位体、PETで検出可能な同位体、SPECTで検出可能な同位体、親和性作用物質、T細胞、又はNK細胞である、請求項1に記載の方法。
- 前記T細胞は、エクトドメインとしてscFvを有するキメラ受容体を発現するT細胞であり、前記合成抗体はscFvである、請求項4に記載の方法。
- 前記NK細胞は、高親和性のFcγ受容体(CD16)を発現するNK細胞であり、前記合成抗体はIgGであって、かつ、高親和性のFcγ受容体を介してNK細胞に結合される、請求項4に記載の方法。
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PCT/US2016/029244 WO2016172722A1 (en) | 2015-04-23 | 2016-04-25 | Cancer neoepitopes |
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