JP2021050164A - 癌免疫増強剤、及びそれを含有する増強抗癌剤 - Google Patents
癌免疫増強剤、及びそれを含有する増強抗癌剤 Download PDFInfo
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Abstract
Description
以下のようにして、マウスPDAC(膵管腺癌)細胞株を用いた癌転移モデルを作製した後、試験を行った。
先ず、0日目に、マウスPDAC細胞株としてPAN02細胞株の2.5×106個/200μlのリン酸緩衝生理食塩水(PBS)液を、C57BL/6L雄マウスに脾臓内注射し、7日間飼育して、肝転移モデルを作製した。
7日目から37日目まで定間隔で計9回、5群のそれぞれに被検液A〜EのPBS液を腹腔内注射処理し、各マウスを死亡するまで又は最大71日目まで飼育した。1〜3回目投与と4回目投与以降との被検液A〜Eの組成を以下に示す。ゲムシタビン(GEM)はBecton Dickinson社製で1mg/100μL、抗PD−1抗体(anti-PD1)はBecton Dickinson社製で200μg/200μL又は150μg/150μLで、抗Ly6c抗体(anti-Ly6c)はBecton Dickinson社製で200μg/200μLを用いた。
・被検液A〜Eについて
被検液A(比較例1):1群中n=7、PBS液のみ(ネガティブコントロール)
被検液B(比較例2):1群中n=7、GEM含有液(ポジティブコントロール)
被検液C(実施例1):1群中n=6、GEM+anti-PD1
被検液D(実施例2):1群中n=7、GEM+anti-Ly6c
被検液E(実施例3):1群中n=6、GEM+anti-Ly6c+anti-PD1
・1〜3回目投与まで
GEM濃度 :1mg/100μL
Anti-Ly6c濃度:200μg/200μL
Anti-PD1濃度 :200μg/200μL
・4回目投与以降
GEM濃度 :1mg/100μL
Anti-Ly6c濃度:200μg/200μL
Anti-PD1濃度 :150μg/150μL
前記の実施例2(被検液D使用)及び実施例3(被検液E使用)、並びに比較例1(被検液A使用)と同様なモデルにおけるマウスの38日目に、マウス抹消血液のリンパ中のヘルパー細胞であるCD4+T細胞及びキラー細胞であるCD8+T細胞の割合と、そのCD4+T細胞中及びCD8+T細胞中でのPD−1陽性細胞の割合とについて、検討した。BD AccuriTM C6 Cytometer (BD Biosciences社製の商品名)を用いて、各試料を処理し、FlowJo (登録商標) V10 software (Tree Star社製)によりデータを解析した。
前方散乱光(forward scatter;FSC)と測方散乱光(side scatter;SSC)の組合せから得られるパラメーターとするサイトグラムによるゲーティングにより、求めた。その結果を、図2(a)〜(b)及び(c)〜(d)に示す。
Claims (8)
- 白血球表面抗原アンタゴニストを、免疫修飾抗癌剤の薬効増強有効成分として、含有していることを特徴とする、癌免疫増強剤。
- 前記白血球表面抗原アンタゴニストが、抗Ly6c抗体及び/又は抗PD−1抗体であることを特徴とする請求項1に記載の癌免疫増強剤。
- 請求項1又は2に記載の癌免疫増強剤と、免疫修飾抗癌剤とを組み合わせたものであり、前記免疫修飾抗癌剤の薬効が増強されていることを特徴とする増強抗癌剤。
- 前記免疫修飾抗癌剤が、代謝拮抗薬であることを特徴とする請求項3に記載の増強抗癌剤。
- 前記代謝拮抗薬が、ゲムシタビン、5−フルオロウラシル、テガフール、テガフールとギメラシルとオテラシルカリウムとの併合剤、イリノテカン、及びオキサリプラチンから選ばれる少なくとも何れかであることを特徴とする請求項4に記載の増強抗癌剤。
- 前記免疫修飾抗癌剤と、抗Ly6c抗体及び抗PD−1抗体とを、含有することを特徴とする請求項3〜5の何れかに記載の増強抗癌剤。
- 膵臓・胆道系癌の治療薬であることを特徴とする請求項3〜6の何れかに記載の増強抗癌剤。
- 前記膵臓・胆道系癌が、膵臓癌であることを特徴とする請求項7に記載の増強抗癌剤。
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