JP4281071B1 - Vγ9Vδ2T細胞の増殖剤、活性化Vγ9Vδ2T細胞の製造方法およびこれらの利用 - Google Patents
Vγ9Vδ2T細胞の増殖剤、活性化Vγ9Vδ2T細胞の製造方法およびこれらの利用 Download PDFInfo
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- JP4281071B1 JP4281071B1 JP2008180749A JP2008180749A JP4281071B1 JP 4281071 B1 JP4281071 B1 JP 4281071B1 JP 2008180749 A JP2008180749 A JP 2008180749A JP 2008180749 A JP2008180749 A JP 2008180749A JP 4281071 B1 JP4281071 B1 JP 4281071B1
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Abstract
【解決手段】少なくとも、ゾレドロネート等のビスホスホネート、インターロイキン2およびインターロイキン18を含む、Vγ9Vδ2T細胞の増殖剤と増殖キット。また、該T細胞を含む医薬品。
【選択図】図1
Description
本発明にかかるVγ9Vδ2T細胞の増殖剤は、ビスホスホネート、インターロイキン2およびインターロイキン18を必須成分として含んでいる。
本発明にかかる活性化Vγ9Vδ2T細胞の製造方法は、Vγ9Vδ2T細胞を、少なくともビスホスホネート、インターロイキン2およびインターロイキン18を用いて刺激することによって、活性化Vγ9Vδ2T細胞、すなわち強い抗腫瘍作用およびサイトカイン産生能を有するVγ9Vδ2T細胞を得る方法である。
健康な成人より末梢血を採取し、Ficoll-Hypaque密度勾配遠心法を用いて(条件:室温(摂氏25℃)で、スイングローターTS−7(トミー精工)を用い、2000rpm、20分間遠心)、末梢血単核球(以下「PBMC」と略記する)を分離した。
(実施例2−1:表面抗原NKG2Dの発現)
上記のようにIL−2とゾレドロネートとIL−18とを用いて刺激し、増殖させたVγ9Vδ2T細胞(活性化Vγ9Vδ2T細胞)についてフローサイトメトリーを用いて解析したところ、抗腫瘍作用に重要な役割を持つNKG2Dを強く発現していた。それゆえ、強い抗腫瘍作用をもつことが示唆された。図3は、活性化Vγ9Vδ2T細胞上のNKG2Dの発現を示すものである。図3の(a)は図2の(g)と同じであり、丸囲みした部分はVγ9Vδ2T細胞である。図3の(b)より、IL−2とゾレドロネートとIL−18とを用いて刺激したVδ2T細胞がNKG2Dを強く発現していることが分かる。
腫瘍細胞に対する殺細胞活性は、様々な腫瘍細胞(ターゲット)とVγ9Vδ2T細胞(エフェクター)とを様々な比率で一晩共培養後、放出されたセリンエステラーゼをBLT法によって測定し、溶解した標的腫瘍細胞の割合を計算することにより評価した。中皮腫から樹立した3種類の腫瘍細胞(MESO−1、MESO−4,MSTO-211H)、正常中皮細胞であるMet5A、骨肉腫より樹立した細胞に対し、エフェクター:ターゲットの細胞数比1:1、3:1、10:1で、Vγ9Vδ2T細胞の殺腫瘍細胞活性を測定した。
様々な条件で培養したVγ9Vδ2T細胞の培養液の上清について、ELISA法を用いてサイトカイン(IFN−γ、TNF、GM−CSFなど)産生を測定した。図5は、ゾレドロネートとIL−2とIL−18とを加え、1週間培養したVγ9Vδ2T細胞によるIFN‐γおよびTNFαの産生を示すものである。
in vivoにおける抗腫瘍効果の測定は、NODscidマウスにヒト中皮腫由来腫瘍細胞を2x106個皮下に移植し、腫瘍の直径が約0.5cmになったところで107個のVγ9Vδ2T細胞を約1週間に1度の割合で尾静脈より注射し、適当な間隔で腫瘍の大きさを測定することで評価した。なお、腫瘍の大きさ(体積)は、(腫瘍の長径)×(腫瘍の短径)2×π÷6により計算した。図6は、in vivoにおける活性化Vγ9Vδ2T細胞の抗腫瘍効果の測定結果を示すものである。
Claims (3)
- 少なくともゾレドロネート、インターロイキン2およびインターロイキン18を含むことを特徴とするVγ9Vδ2T細胞の増殖剤。
- Vγ9Vδ2T細胞を、少なくともゾレドロネート、インターロイキン2およびインターロイキン18を用いて刺激することを特徴とする、活性化Vγ9Vδ2T細胞の製造方法。
- 少なくとも、Vγ9Vδ2T細胞、ゾレドロネート、インターロイキン2およびインターロイキン18を備えることを特徴とするVγ9Vδ2T細胞の増殖キット。
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US12/316,973 US7749760B2 (en) | 2008-07-10 | 2008-12-17 | Vγ9Vδ2 T cell proliferation agent, method for producing activated Vγ9Vδ2 T cells, and uses thereof |
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WO2011096504A1 (ja) * | 2010-02-08 | 2011-08-11 | 株式会社日本バイオセラピー研究所 | Nk細胞強化型血液製剤の製造方法 |
CN109529050A (zh) * | 2018-12-07 | 2019-03-29 | 广州市妇女儿童医疗中心 | Vγ9δ2T细胞、治疗肺癌的药物ZOL和hMSH2协同作用的应用 |
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CN103555666A (zh) * | 2013-07-17 | 2014-02-05 | 浙江大学 | 一种提高Vγ9Vδ2T细胞扩增效率及活性的培养方法 |
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JPWO2006006720A1 (ja) | 2004-07-13 | 2008-05-01 | 株式会社メディネット | γδT細胞の培養方法、γδT細胞及び治療・予防剤 |
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WO2011096504A1 (ja) * | 2010-02-08 | 2011-08-11 | 株式会社日本バイオセラピー研究所 | Nk細胞強化型血液製剤の製造方法 |
JP5766619B2 (ja) * | 2010-02-08 | 2015-08-19 | 株式会社日本バイオセラピー研究所 | Nk細胞強化型血液製剤の製造方法 |
CN109529050A (zh) * | 2018-12-07 | 2019-03-29 | 广州市妇女儿童医疗中心 | Vγ9δ2T细胞、治疗肺癌的药物ZOL和hMSH2协同作用的应用 |
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