内容紹介
Targeting the PD-1/PD-L1 Immune Checkpoint Signal―A New Treatment Strategy for Cancer
Summary
Recent studies have revealed that tumor cells can acquire several mechanisms to evade host immunity in the tumor microenvironment, called cancer immune escape. One of the most important mechanisms in this system is an immunosuppressive co-signal, called immune checkpoint, in the programmed cell death-1(PD-1)/programmed death-ligand 1(PD-L1)pathway. PD-1 is mainly expressed on activated T cells, while PD-L1 is frequently expressed on tumor cells. Inhibition of the interaction between PD-1 and PD-L1 enhances T-cell response and mediates antitumor activity. Several clinical trials by several institutions and pharmaceutical companies in the world have shown the antitumor efficacy of PD-1/PD-L1 signal blockade in patients with some solid and hematological malignancies. Production of some drugs for use in anti-PD-1 therapies are on the verge of completion. Herein, we provide a background about the PD-1/PD-L1 signal and describe some previously performed foreign clinical trials, including a trial in our department.
要旨
近年のがん免疫学研究の発展により,がん微小環境における「がん免疫逃避機構」の存在が明らかとなり,さらにその中心的経路の一つとして,T細胞性免疫の機能抑制にかかわる免疫抑制性副シグナル(免疫チェックポイントとも呼ばれている)PD-1/PD-L1経路とその阻害薬が注目されている。現在,このPD-1/PD-L1経路の阻害薬は,複数の製薬会社や研究施設によって世界中で多くの固形がんや血液腫瘍を対象に臨床試験が行われており,メラノーマに対しては薬事承認された薬剤もでてきている。そこで本稿では,PD-1/PD-L1経路の基礎的背景と当科での治験ならびに国内外での治験の動向について概説する。
目次
Summary
Recent studies have revealed that tumor cells can acquire several mechanisms to evade host immunity in the tumor microenvironment, called cancer immune escape. One of the most important mechanisms in this system is an immunosuppressive co-signal, called immune checkpoint, in the programmed cell death-1(PD-1)/programmed death-ligand 1(PD-L1)pathway. PD-1 is mainly expressed on activated T cells, while PD-L1 is frequently expressed on tumor cells. Inhibition of the interaction between PD-1 and PD-L1 enhances T-cell response and mediates antitumor activity. Several clinical trials by several institutions and pharmaceutical companies in the world have shown the antitumor efficacy of PD-1/PD-L1 signal blockade in patients with some solid and hematological malignancies. Production of some drugs for use in anti-PD-1 therapies are on the verge of completion. Herein, we provide a background about the PD-1/PD-L1 signal and describe some previously performed foreign clinical trials, including a trial in our department.
要旨
近年のがん免疫学研究の発展により,がん微小環境における「がん免疫逃避機構」の存在が明らかとなり,さらにその中心的経路の一つとして,T細胞性免疫の機能抑制にかかわる免疫抑制性副シグナル(免疫チェックポイントとも呼ばれている)PD-1/PD-L1経路とその阻害薬が注目されている。現在,このPD-1/PD-L1経路の阻害薬は,複数の製薬会社や研究施設によって世界中で多くの固形がんや血液腫瘍を対象に臨床試験が行われており,メラノーマに対しては薬事承認された薬剤もでてきている。そこで本稿では,PD-1/PD-L1経路の基礎的背景と当科での治験ならびに国内外での治験の動向について概説する。