内容紹介
Summary
Cancer antigens are classified into shared antigens and tumor-specific antigens based on their expression pattern or immunogenicity. Neo-antigens are defined as a subset of tumor-specific antigens generated by non-synonymous mutations, Indel gene mutation or gene fusions, presented by major histocompatibility complex molecules that were recognized by effector CD8+ T cells. Cancer cells with inherent genetic instability form abnormal proteins that have not been previously recognized by the immune system and these proteins become highly immunogenic antigens(neo-antigens)that can spontaneously trigger CD8+ T cell responses. Cancer cells that present extremely immunogenic neo-antigens are eliminated from the host through the process of carcinogenesis. Therefore, recognition of neo-antigens could be an important subject of the clinical utility of both neo-antigen cancer vaccine and adoptive TCR-T cell therapy as cancer immunotherapies. Furthermore, monitoring the quantity and quality of the neo-antigen derived in each patient could deduce the clinical response to immune checkpoint inhibitors such as anti-PD-1 therapy in various cancers. Here we review the evidence for the relevance of tumor neo-antigens and host immune response. We discuss the utility as a biomarker for cancer immunotherapy using the neo-antigen expression in tumor tissues and the development of neo-antigen-targeted cancer vaccine and T cell mediated therapies.
要旨
がん抗原は,その発現パターンもしくは免疫原性から共通抗原とがん特異抗原に分別される。ネオ抗原は様々な遺伝子異常に基づくがん特異的な抗原であり,免疫原性は非常に高く,その発現パターンから胸腺における免疫寛容を免れており,抗腫瘍活性を有するCD8+ T細胞が誘導できる。そのため,ネオ抗原は宿主の免疫応答を惹起できるがん抗原であると同時に,それらの発現を解析することでがんに対する免疫応答を推測できる可能性がある。がんの遺伝子異常のタイプには一塩基置換を伴う遺伝子変異や欠失挿入変異,融合変異などがあり,それらの遺伝子異常を基にしたネオ抗原の免疫原性が現在解析されている。上記のネオ抗原を用いたがん治療は,ネオ抗原ワクチンをはじめTCR-T細胞療法などに応用されようとしている。また,ネオ抗原の質と量は免疫チェックポイント阻害剤の奏効バイオマーカーとして注目を浴びている。
目次
Cancer antigens are classified into shared antigens and tumor-specific antigens based on their expression pattern or immunogenicity. Neo-antigens are defined as a subset of tumor-specific antigens generated by non-synonymous mutations, Indel gene mutation or gene fusions, presented by major histocompatibility complex molecules that were recognized by effector CD8+ T cells. Cancer cells with inherent genetic instability form abnormal proteins that have not been previously recognized by the immune system and these proteins become highly immunogenic antigens(neo-antigens)that can spontaneously trigger CD8+ T cell responses. Cancer cells that present extremely immunogenic neo-antigens are eliminated from the host through the process of carcinogenesis. Therefore, recognition of neo-antigens could be an important subject of the clinical utility of both neo-antigen cancer vaccine and adoptive TCR-T cell therapy as cancer immunotherapies. Furthermore, monitoring the quantity and quality of the neo-antigen derived in each patient could deduce the clinical response to immune checkpoint inhibitors such as anti-PD-1 therapy in various cancers. Here we review the evidence for the relevance of tumor neo-antigens and host immune response. We discuss the utility as a biomarker for cancer immunotherapy using the neo-antigen expression in tumor tissues and the development of neo-antigen-targeted cancer vaccine and T cell mediated therapies.
要旨
がん抗原は,その発現パターンもしくは免疫原性から共通抗原とがん特異抗原に分別される。ネオ抗原は様々な遺伝子異常に基づくがん特異的な抗原であり,免疫原性は非常に高く,その発現パターンから胸腺における免疫寛容を免れており,抗腫瘍活性を有するCD8+ T細胞が誘導できる。そのため,ネオ抗原は宿主の免疫応答を惹起できるがん抗原であると同時に,それらの発現を解析することでがんに対する免疫応答を推測できる可能性がある。がんの遺伝子異常のタイプには一塩基置換を伴う遺伝子変異や欠失挿入変異,融合変異などがあり,それらの遺伝子異常を基にしたネオ抗原の免疫原性が現在解析されている。上記のネオ抗原を用いたがん治療は,ネオ抗原ワクチンをはじめTCR-T細胞療法などに応用されようとしている。また,ネオ抗原の質と量は免疫チェックポイント阻害剤の奏効バイオマーカーとして注目を浴びている。