内容紹介
Summary
Near infrared photoimmunotherapy(NIR-PIT)is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IRDye700DX(IR700), to a monoclonal antibody(mAb)targeting cell-surface molecules. NIR-PIT targeting EGFR using the cetuximab-IR700 conjugate is now in transition to fast-track global Phase Ⅲ clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highly-selective necrotic/immunogenic cell death(ICD)only in target-positive, mAb-IR700-bound cancer cells. This cell death occurs as early as 1 minute after exposure to NIR light. Meanwhile, immediately adjacent target-negative cells are unharmed. ICD induced by NIR-PIT promoted maturation of immature dendritic cells(DCs)to maturated DCs that primed cytotoxic T-cells to react with cancer-related antigens released from destroyed cancer cells. Inhibition of immuno-checkpoints including PD-1/PD-L1 axis or CTLA-4 is one of several major methods for enhancing cytotoxicity of tumor-infiltrating T-cells. In this section, I will also discuss NIR-PIT combined with an immuno-checkpoint inhibitor that could treat not only local tumors but also distant untreated metastatic tumors without recurrence in some syngeneic cancer models. Additionally, NIR-PIT to a local tumor combined with local tumor-infiltrating negative-regulatory T-cells by CD25-targeted NIR-PIT that is another major methods for enhancing cytotoxicity of tumor-infiltrating T-cells similarly operated in different tumor models. The regimens of NIR-PIT combined with methods for enhancing host tumor immunity could cure primary and metastatic tumor and yield vaccination effect against treated cancer cells that would be the ultimate form of NIR-PIT in oncology clinic.
要旨
超細胞特異的ながん治療は,がんに対しては強力でありつつ患者の体にはやさしい治療になり得る。本稿では,まず分子イメージング技術の新たな進化形である超細胞選択的がん治療,「近赤外光線免疫療法」の化学,物理学,生物学を統合した理論に基づいた開発理念について論じ,さらに従来のがん治療法と比較した優位点について論じる。また,2015年より始まった近赤外光線免疫療法の再発頭頸部扁平上皮がんに対する臨床治験についても少し触れる。加えて,近赤外光線免疫療法の治療対象となるがんの種類,標的分子,病態,さらに近赤外光線免疫療法を免疫抑制細胞に対して用いることで可能になるがんに対する強力な免疫誘導など多様な応用法について論じる。
目次
Near infrared photoimmunotherapy(NIR-PIT)is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IRDye700DX(IR700), to a monoclonal antibody(mAb)targeting cell-surface molecules. NIR-PIT targeting EGFR using the cetuximab-IR700 conjugate is now in transition to fast-track global Phase Ⅲ clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highly-selective necrotic/immunogenic cell death(ICD)only in target-positive, mAb-IR700-bound cancer cells. This cell death occurs as early as 1 minute after exposure to NIR light. Meanwhile, immediately adjacent target-negative cells are unharmed. ICD induced by NIR-PIT promoted maturation of immature dendritic cells(DCs)to maturated DCs that primed cytotoxic T-cells to react with cancer-related antigens released from destroyed cancer cells. Inhibition of immuno-checkpoints including PD-1/PD-L1 axis or CTLA-4 is one of several major methods for enhancing cytotoxicity of tumor-infiltrating T-cells. In this section, I will also discuss NIR-PIT combined with an immuno-checkpoint inhibitor that could treat not only local tumors but also distant untreated metastatic tumors without recurrence in some syngeneic cancer models. Additionally, NIR-PIT to a local tumor combined with local tumor-infiltrating negative-regulatory T-cells by CD25-targeted NIR-PIT that is another major methods for enhancing cytotoxicity of tumor-infiltrating T-cells similarly operated in different tumor models. The regimens of NIR-PIT combined with methods for enhancing host tumor immunity could cure primary and metastatic tumor and yield vaccination effect against treated cancer cells that would be the ultimate form of NIR-PIT in oncology clinic.
要旨
超細胞特異的ながん治療は,がんに対しては強力でありつつ患者の体にはやさしい治療になり得る。本稿では,まず分子イメージング技術の新たな進化形である超細胞選択的がん治療,「近赤外光線免疫療法」の化学,物理学,生物学を統合した理論に基づいた開発理念について論じ,さらに従来のがん治療法と比較した優位点について論じる。また,2015年より始まった近赤外光線免疫療法の再発頭頸部扁平上皮がんに対する臨床治験についても少し触れる。加えて,近赤外光線免疫療法の治療対象となるがんの種類,標的分子,病態,さらに近赤外光線免疫療法を免疫抑制細胞に対して用いることで可能になるがんに対する強力な免疫誘導など多様な応用法について論じる。