Identification of neoantigens and development of antigen-specific immunotherapy
Identification of neoantigens and development of antigen-specific immunotherapy
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新抗原的鉴定和抗原特异性免疫疗法的开发
DOI：
10.11406/rinketsu.61.1433
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Matsuhita H.
中科院分区：
文献类型：
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作者：
Shinohara S.;Takahashi Y.;Demachi-Okamura A.;Matsuhita H.
携带体细胞突变的癌细胞产生新抗原，所述新抗原在本质上是免疫学上外来的以与自身区分开，显示出高免疫原性，并因此诱导针对癌症的特异性T细胞应答。因此，新抗原有望成为抗癌免疫治疗的有前途的靶点。用于鉴定候选新抗原的一般方法如下：（1）通过全外显子组和RNA测序鉴定非同义突变;（2）基于计算机模拟MHC配体预测算法预测来自突变的新抗原;（3）使用肿瘤浸润T细胞或外周血单核细胞验证针对候选新抗原的特异性T细胞应答。在血液恶性肿瘤中，几种新抗原已被鉴定为重要的治疗靶点。与实体恶性肿瘤相比，移码突变和产生新抗原的融合基因的发生率很高。在急性髓系白血病中，常观察到一种源自核磷蛋白I移码突变的共享新抗原，据报道其在体外和体内诱导特异性免疫应答。我们应该检查新抗原作为新的免疫治疗的可能靶点，尽管有几个问题需要解决的临床应用。
Cancer cells harboring somatic mutations give rise to neoantigens, which are immunologically foreign in nature to be distinguished from itself, showing high immunogenicity and, thus, induce specific T-cell responses against cancer. Therefore, neoantigens are expected to be promising targets for anti-cancer immunotherapy. The general methods used to identify candidate neoantigens are as follows:(1) non-synonymous mutations are identified by whole exome and RNA sequencing;(2) neoantigens from the mutations are predicted based on in silico MHC ligand prediction algorithm;(3) specific T-cell responses toward the candidate neoantigens are verified using tumor infiltrating T cells or peripheral blood mononuclear cells. In hematological malignancy, several neoantigens have been identified as an important treatment target. In contrast with solid malignancies, the occurrence of frameshift mutations and fusion genes producing neoantigens are high. A shared neoantigen derived from frameshift mutation of nucleophosmin I, which is often observed in acute myeloid leukemia, was reported to induce specific immune responses in vitro and in vivo. We should examine neoantigens as possible target of novel immunotherapy despite several issues to be addressed for clinical application.