IrsiCaixa AIDS Research Institute, Germans Trias i Pujol University Hospital, Badalona, Spain; Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
IrsiCaixa AIDS Research Institute, Germans Trias i Pujol University Hospital, Badalona, Spain; Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
ESMO Open. 2020 Apr;4(Suppl 3):e000684. doi: 10.1136/esmoopen-2020-000684.
The success of cancer therapies with immune checkpoint inhibitors is transforming the treatment of patients with cancer and fostering cancer research. Therapies that target immune checkpoint inhibitors have shown unprecedented rates of durable long-lasting responses in patients with various cancer types, but only in a fraction of patients. Thus, novel approaches are needed to make immunotherapy more precise and also less toxic. The advances of next-generation sequencing technologies have allowed fast detection of somatic mutations in genes present in the exome of an individual tumour. Targeting neoantigens, the mutated peptides expressed only by tumour cells, may enable antitumour T-cell responses and tumour destruction without causing harm to healthy tissues. Currently, neoantigens can be identified in tumour clinical samples by using genomic-based computational tools. The two main treatment modalities targeting neoantigens that have been investigated in clinical trials are personalised vaccines and tumour infiltrating lymphocytes-based adoptive T-cell therapy. In this mini review, we discuss the promises and challenges for using neoantigens as emergent targets to personalise and guide cancer immunotherapy in a broader set of cancers.
癌症免疫检查点抑制剂治疗的成功正在改变癌症患者的治疗方式,并促进癌症研究。针对免疫检查点抑制剂的治疗方法在各种癌症类型的患者中显示出了前所未有的持久缓解率,但只有一部分患者受益。因此,需要新的方法使免疫疗法更精确,同时毒性更小。下一代测序技术的进步使得能够快速检测个体肿瘤外显子中存在的体细胞突变。针对新抗原,即仅由肿瘤细胞表达的突变肽,可能会引发抗肿瘤 T 细胞反应和肿瘤破坏,而不会对健康组织造成伤害。目前,可以使用基于基因组的计算工具在肿瘤临床样本中鉴定新抗原。在临床试验中研究的针对新抗原的两种主要治疗方式是个性化疫苗和肿瘤浸润淋巴细胞过继 T 细胞治疗。在这篇综述中,我们讨论了将新抗原作为新兴靶点用于更广泛的癌症患者的个体化和指导癌症免疫治疗的前景和挑战。