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IMMUNE FUNCTION EVALUATION METHOD AND ELISA SYSTEM THEREFOR

Foreign code F190009803
File No. S2017-1058-C0
Posted date May 8, 2019
Country WIPO
International application number 2018JP033161
International publication number WO 2019049974
Date of international filing Sep 7, 2018
Date of international publication Mar 14, 2019
Priority data
  • P2017-172593 (Sep 8, 2017) JP
Title IMMUNE FUNCTION EVALUATION METHOD AND ELISA SYSTEM THEREFOR
Abstract The purpose of the present invention is to develop a method capable of evaluating T-cell immune function. A method for evaluating T-cell immune function, said method characterized by detecting and quantifying soluble PD-L1 having a capacity for binding with PD-1. An ELISA system used for detecting and quantifying bsPD-L1, said system including: a means that includes a carrier with the solid-phased PD-1 protein thereon, and reacts the carrier and a test sample; and a means for detecting and quantifying, as bsPD-L1, soluble PD-L1 binded to the carrier.
Outline of related art and contending technology BACKGROUND ART
T cell immune related disease condition, as well as cancer, infection, autoimmune disease, allergy, rejection at the time of implantation, and a wide range of life-style related diseases. Immune function of an individual is currently in clinical applications, in particular T cell function there is no evaluation means equal to. Current, are routinely performed in clinical blood as an index associated with an inspection, the number of white blood cells, white blood cell fractions, immunoglobulin, CRP and the like, of the individual inspection items are T cell function cannot be evaluated. T cell function in the molecule control, PD-1/known PD-L1.
The PD-1, T cells express a surface membrane protein or the like (Patent Document 1, 2). PD-1 as a ligand, identified and PD-L2 PD-L1 and, of these molecules in combination with T cell function PD-1 can be suppressed, to modulate the suppressed immune response are known. In addition, virus infection or cancer cells that express a ligand by PD-1, via binding of the PD-1, to escape from the host immune surveillance has been known.
One of the ligands of these PD-1 PD-L1 is, expressing the cell surface and the film type, is present in the blood is present in the soluble. Film type PD-L1 is, inhibition of decomposition by glycosylation N- stabilized, and increase the binding capacity of the PD-1 has been known (Non-Patent Document 1). On the other hand, in PD-L1 nonsupressor, glycosylated is what is known, the meaning is not apparent. The signal PD-1/PD-L1 have been developed as attention is paid to the agent, the antibody is anti-PD-1 nivolumab formulation (product name: opujibo) and the like.
Nivolumab is, in the molecule to inhibit immune checkpoint by PD-1, releases the brakes of the immune system, increased anti-tumor immune response against cancer effect. Nivolumab of the response rate, and from about 20 and 30%, a high sensitivity low patient group of patients is divided into a current. For predicting drug sensitivity in a variety of attempts have been made and, as one example, tumor tissue by examining the expression of a PD-L1, an attempt is made to make a diagnosis of whether or not the adaptation is. In addition, the anti-antibody treatment from the patient before and after the PD-1 using a blood sample, the blood is present in the PD-L1 nonsupressor PD-1 the therapeutic effect of the anti-biomarker antibody therapy may be distinguished and have been studied. In addition, the relationship between PD-L1 nonsupressor prognosis have been investigated. For example, non-small cell lung cancer patients in the test target 109 example, tissue in the same manner as PD-L1, the expression of the prognosis nonsupressor PD-L1 an inverse correlation (nonsupressor PD-L1 value group is compared with the low-value group and a poor prognosis) has been reported (Non-Patent Document 2). However, the expression of the prognosis of cancer in tissue and immune or PD-L1 checkpoint inhibitor will be described in the context of an overall response rate, consistent with the current view is not obtained in the (non-patent document 5 from 3). In addition, immunohistological examination, biopsy sampling portion of the engine and affected by variations in inspection, and quantification is standardized is difficult.
Scope of claims (In Japanese)請求の範囲 [請求項1]
 被験試料とPD-1を反応させる工程、およびPD-1と結合した可溶型PD-L1を「PD-1結合能を有する可溶型PD-L1(bsPD-L1)」として検出・定量する工程を含む、T細胞免疫機能の評価方法。

[請求項2]
 bsPD-L1が、糖鎖修飾されたPD-L1である請求項1記載の評価方法。

[請求項3]
 被験試料が、生体由来試料である請求項1または2に記載の評価方法。

[請求項4]
 さらに、抗PD-L1抗体と前記被験試料とを反応させ、被験試料中の可溶型PD-L1(sPD-L1)を検出・定量する工程を含み、結果を合わせて評価を行う請求項1から3のいずれか1項に記載の評価方法。

[請求項5]
 T細胞免疫が関与する疾患における病態、予後および治療効果を評価する工程、または該評価を補助する工程をさらに含む、請求項1から4のいずれか1項に記載の評価方法。

[請求項6]
 T細胞免疫が関与する疾患ががんである、請求項5に記載の評価方法。

[請求項7]
 免疫療法の適応診断、治療効果および副作用予測を評価する工程、または該評価を補助する工程をさらに含む、請求項1から4のいずれか1項に記載の評価方法。

[請求項8]
 被験試料中の、bsPD-L1の量または濃度がカットオフ値以上の場合に予後が良好であると予測し得る、請求項6に記載の評価方法。

[請求項9]
 bsPD-L1を含む、T細胞免疫機能評価用バイオマーカー。

[請求項10]
 bsPD-L1およびsPD-L1を含む、T細胞免疫機能評価用のバイオマーカーの組合せ。

[請求項11]
 T細胞免疫機能評価が、T細胞免疫が関与する疾患における病態、予後および治療効果を評価する為のものである、請求項9記載のバイオマーカーまたは請求項10記載のバイオマーカーの組合せ。

[請求項12]
 T細胞免疫機能評価が、免疫療法の適応診断、治療効果および副作用予測を評価する為のものである、請求項9記載のバイオマーカーまたは請求項10記載のバイオマーカーの組合せ。

[請求項13]
 被験試料中の、bsPD-L1を検出・定量する為のシステムであって、PD-1タンパク質を含み、該タンパク質と被験試料とを反応させる手段および該タンパク質に結合した可溶型PD-L1をbsPD-L1として検出・定量する為の手段を含むシステム。

[請求項14]
 さらに、抗PD-L1抗体を含み、該抗体と被験試料とを反応させる手段および該抗体に結合した可溶型PD-L1を検出・定量する為の手段を含む請求項13記載のシステム。

[請求項15]
 ELISAシステムである請求項13または14記載のシステム。

[請求項16]
 T細胞免疫が関与する疾患における病態、予後および治療効果を評価する、または評価を補助する為の請求項13から15のいずれか1項に記載のシステム。

[請求項17]
 免疫療法の適応診断、予後、治療効果および副作用予測を評価する、または評価を補助する為の請求項13から15のいずれか1項に記載のシステム。

[請求項18]
 PD-1タンパク質が固相化された担体および該担体に結合した可溶型PD-L1をbsPD-L1として検出する為の検出用マーカーを含み、任意で抗PD-L1抗体が固相化された担体および該担体に結合した可溶型PD-L1をsPD-L1として検出する為の検出用マーカーを含んでなるELISAキット。

[請求項19]
 生体由来試料中の可溶型PD-L1を脱グリコシル化処理する工程、および該工程で得られた可溶型PD-L1の脱グリコシル化のパターンを解析する工程を含む、T細胞免疫が関与する疾患における病態、予後および治療効果を評価する、または評価を補助する方法。

[請求項20]
 生体由来試料中の可溶型PD-L1を脱グリコシル化処理する工程、および該工程で得られた可溶型PD-L1の脱グリコシル化のパターンを解析する工程を含む、免疫療法の適応診断、治療効果および副作用予測を評価する、または評価を補助する方法。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, JAPAN
  • NIPPON MEDICAL SCHOOL FOUNDATION
  • Inventor
  • IWAI, Yoshiko
  • TAKEUCHI, Masahiro
  • DOI, Tomomitsu
IPC(International Patent Classification)

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