CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy.
Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy.
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免疫检查点阻断(ICB)疗法的临床获益已被广泛报道。在癌症患者中,研究人员已证明抗肿瘤细胞毒性T细胞的临床潜力,这些T细胞可通过ICB被重新激活或增强。与自身抗原相比,源自肿瘤体细胞突变的新抗原被认为是肿瘤中理想的免疫靶点。候选肿瘤新抗原可通过免疫基因组学或免疫肽组学方法进行鉴定。新抗原的鉴定揭示了若干临床相关性要点。例如,肿瘤突变负荷(TMB)可能是免疫治疗的指标。在多种癌症中,伴随新抗原负荷的突变率可能提示免疫治疗的效果。此外,错配修复缺陷型肿瘤可通过ICB治疗中的T细胞被清除。因此,使用疫苗或过继性T细胞转移靶向新抗原的免疫治疗是潜在的创新策略。然而,确定最佳表位仍需大量努力。在本综述中,我们总结了新抗原鉴定方面的最新进展,并讨论了基于新抗原的临床前和临床研究。我们还讨论了在这些新治疗策略的临床应用得以实现之前仍需解决的问题。
The clinical benefits of immune checkpoint blockage (ICB) therapy have been widely reported. In patients with cancer, researchers have demonstrated the clinical potential of antitumor cytotoxic T cells that can be reinvigorated or enhanced by ICB. Compared to self-antigens, neoantigens derived from tumor somatic mutations are believed to be ideal immune targets in tumors.
Candidate tumor neoantigens can be identified through immunogenomic or immunopeptidomic approaches. Identification of neoantigens has revealed several points of the clinical relevance. For instance, tumor mutation burden (TMB) may be an indicator of immunotherapy. In various cancers, mutation rates accompanying neoantigen loads may be indicative of immunotherapy.
Furthermore, mismatch repair-deficient tumors can be eradicated by T cells in ICB treatment. Hence, immunotherapies using vaccines or adoptive T-cell transfer targeting neoantigens are potential innovative strategies.
However, significant efforts are required to identify the optimal epitopes. In this review, we summarize the recent progress in the identification of neoantigens and discussed preclinical and clinical studies based on neoantigens.
We also discuss the issues remaining to be addressed before clinical applications of these new therapeutic strategies can be materialized.
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