内容紹介
Summary
Recent advances in cancer immunotherapies, such as immune checkpoint inhibitors(ICIs), have shown some durable clinical responses in patients with various types of advanced cancers. The development of the next-generation sequencing technologies can result in a comprehensive characterization of the human cancer genomes. Personalized immunotherapy and precision cancer medicine might enable the next generation of rational cancer immunotherapy. Conventional cancer vaccines are designed to target tumor-associated antigens(TAAs), which are overexpressed in cancers. However, since TAAs are also expressed in normal tissues, cancer vaccine against TAAs can potentially initiate central and peripheral tolerance responses, which results in low vaccination efficiency. Cancer neoantigens derived from somatic mutations in tumor tissue represent highly immunogenic and can escape from central thymic tolerance. They are suggested to provide tumor specific targets for personalized cancer vaccines. Therefore, neoantigen-based cancer vaccine, which can induce tumor-specific cytotoxic T lymphocytes(CTLs), should be developed. The efficacy of current immunotherapies also remains limited due to the immunosuppressive tumor microenvironment, which leads to CTLs exhaustion or anergy and the escape of tumor cells from immune attack. The combination of neoantigen-based cancer vaccine and ICIs should be a potential therapeutic approach. In this paper, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines.
要旨
免疫チェックポイント阻害剤(ICI)の登場によりがんが免疫で治ることを万人が認めた。さらに遺伝子解析技術の進歩により,がん細胞に特異的な遺伝子変異を各個人のレベルで解析することが可能となり,正に個別化医療が導入されようとしている。従来のがんワクチン療法は,がん細胞に多く発現しているが正常細胞にも少なからず発現を伴う腫瘍関連抗原を標的としていたため,免疫原性が低く効果は限定的であった。一方,がん細胞に生じた腫瘍特異的な遺伝子変異由来抗原であるネオアンチゲンは,本来生体には存在しないため高い免疫原性を有しており,強力な腫瘍特異的T細胞が誘導されると考えられ,ネオアンチゲンを標的としたがんワクチン療法が非常に注目を浴びている。さらに,このワクチン療法を成功させるにはがん微小環境における治療抵抗性因子の制御も必要であり,ICIを含む他の免疫療法と併用して次世代がん治療法となる個別化がん免疫療法を開発していく必要がある。
目次
Recent advances in cancer immunotherapies, such as immune checkpoint inhibitors(ICIs), have shown some durable clinical responses in patients with various types of advanced cancers. The development of the next-generation sequencing technologies can result in a comprehensive characterization of the human cancer genomes. Personalized immunotherapy and precision cancer medicine might enable the next generation of rational cancer immunotherapy. Conventional cancer vaccines are designed to target tumor-associated antigens(TAAs), which are overexpressed in cancers. However, since TAAs are also expressed in normal tissues, cancer vaccine against TAAs can potentially initiate central and peripheral tolerance responses, which results in low vaccination efficiency. Cancer neoantigens derived from somatic mutations in tumor tissue represent highly immunogenic and can escape from central thymic tolerance. They are suggested to provide tumor specific targets for personalized cancer vaccines. Therefore, neoantigen-based cancer vaccine, which can induce tumor-specific cytotoxic T lymphocytes(CTLs), should be developed. The efficacy of current immunotherapies also remains limited due to the immunosuppressive tumor microenvironment, which leads to CTLs exhaustion or anergy and the escape of tumor cells from immune attack. The combination of neoantigen-based cancer vaccine and ICIs should be a potential therapeutic approach. In this paper, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines.
要旨
免疫チェックポイント阻害剤(ICI)の登場によりがんが免疫で治ることを万人が認めた。さらに遺伝子解析技術の進歩により,がん細胞に特異的な遺伝子変異を各個人のレベルで解析することが可能となり,正に個別化医療が導入されようとしている。従来のがんワクチン療法は,がん細胞に多く発現しているが正常細胞にも少なからず発現を伴う腫瘍関連抗原を標的としていたため,免疫原性が低く効果は限定的であった。一方,がん細胞に生じた腫瘍特異的な遺伝子変異由来抗原であるネオアンチゲンは,本来生体には存在しないため高い免疫原性を有しており,強力な腫瘍特異的T細胞が誘導されると考えられ,ネオアンチゲンを標的としたがんワクチン療法が非常に注目を浴びている。さらに,このワクチン療法を成功させるにはがん微小環境における治療抵抗性因子の制御も必要であり,ICIを含む他の免疫療法と併用して次世代がん治療法となる個別化がん免疫療法を開発していく必要がある。