Karasaki Takahiro, Nakajima Jun, Kakimi Kazuhiro
Dept. of Thoracic Surgery, The University of Tokyo Hospital.
Gan To Kagaku Ryoho. 2016 Jul;43(7):791-7.
During cancer progression, many somatic mutations accumulate in cancer cells. Antigens derived from tumor-specific mutated genes are primary sources ofneoantigens in cancer immunology. As compared with non-mutated self-antigens, neoantigens are thought to have higher antigenicity, and are expected to be ideal targets for tumor rejection. Recent studies demonstrate that T cells recognize neoantigens and elicit immune responses against tumor cells. The importance ofneoantigens in cancer immunity has been well acknowledged, and development ofneoantigen -targeted cancer immunotherapy is in progress worldwide. High-throughput detection ofsomatic mutations by whole-exome sequencing is combined with computational algorithm for MHC-peptide binding affinity to predict potential neoantigens. After the antigenicity is confirmed by immunological assays, personalized vaccines targeting the identified neoantigens will be generated with peptides, dendritic cells, or RNAs. Such neoantigen-targeted cancer vaccines are being developed for practical use. In fact, several clinical trials have already been initiated in Europe and the US.
在癌症进展过程中,癌细胞会积累许多体细胞突变。源自肿瘤特异性突变基因的抗原是癌症免疫学中新抗原的主要来源。与未突变的自身抗原相比,新抗原被认为具有更高的抗原性,有望成为肿瘤排斥的理想靶点。最近的研究表明,T细胞能够识别新抗原并引发针对肿瘤细胞的免疫反应。新抗原在癌症免疫中的重要性已得到广泛认可,针对新抗原的癌症免疫疗法正在全球范围内开展。通过全外显子测序进行体细胞突变的高通量检测,并结合用于预测MHC-肽结合亲和力的计算算法,来预测潜在的新抗原。通过免疫分析确认抗原性后,将使用肽、树突状细胞或RNA生成针对已鉴定新抗原的个性化疫苗。这种针对新抗原的癌症疫苗正在开发以供实际使用。事实上,欧美已经启动了多项临床试验。