Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biochemistry, Berlin, Germany.
Front Immunol. 2022 Feb 21;13:849863. doi: 10.3389/fimmu.2022.849863. eCollection 2022.
Proteasome generates spliced peptides by ligating two distant cleavage products in a reverse proteolysis reaction. The observation that CD8+ T cells recognizing a spliced peptide induced T cell rejection in a melanoma patient following adoptive T cell transfer (ATT), raised some hopes with regard to the general therapeutic and immune relevance of spliced peptides. Concomitantly, the identification of spliced peptides was also the start of a controversy with respect to their frequency, abundancy and their therapeutic applicability. Here I review some of the recent evidence favoring or disfavoring an immune relevance of splicetopes and discuss from a theoretical point of view the potential usefulness of tumor specific splicetopes and why against all odds it still may seem worth trying to identify such tumor and patient-specific neosplicetopes for application in ATT.
蛋白酶体通过在反向蛋白水解反应中连接两个遥远的切割产物来产生剪接肽。观察到，在接受过继性 T 细胞转移（ATT）后，识别剪接肽的 CD8+T 细胞会引发黑色素瘤患者的 T 细胞排斥反应，这给人们带来了一些希望，即剪接肽具有普遍的治疗和免疫相关性。同时，剪接肽的鉴定也是一个有争议的问题，涉及到它们的频率、丰度及其治疗适用性。在这里，我回顾了一些最近的证据，这些证据支持或不支持剪接表位的免疫相关性，并从理论角度讨论了肿瘤特异性剪接表位的潜在有用性，以及尽管存在各种困难，但尝试鉴定这种肿瘤和患者特异性的新剪接表位并将其应用于 ATT 仍然可能是值得的。
