肿瘤细胞治疗研究
英文原题：Generation of a highly versatile TCR bispecific scaffold optimized for targeting tumor-specific peptide-HLA antigens.
将T淋巴细胞重定向至癌细胞是过去几年肿瘤学领域最有前景的治疗理念之一，并已促使过继性细胞治疗（ACT）和T细胞衔接双特异性（TEB）分子获得多项监管批准。
将T淋巴细胞重定向至癌细胞是过去几年肿瘤学领域最有前景的治疗理念之一，已促成过继性细胞治疗（ACT）和T细胞衔接双特异性（TEB）分子的多项监管批准。然而，进展主要集中于血液系统适应症，靶向所谓的谱系抗原（即CD19、CD20、BCMA）。靶向肽-HLA抗原（pHLA）已被提出作为克服实体瘤中合适表面抗原匮乏的一种策略，但特异性靶向这类低拷贝且高度混杂抗原的技术障碍迄今阻碍了其在更广泛患者群体中的应用。我们在此描述TCER（T细胞衔接受体）的成功开发，这是一种新型且高度通用的基于T细胞受体（TCR）的TEB，具有优化的体内疗效、耐受性、血浆半衰期和稳定性特征，可广泛用于肿瘤学及其他领域靶向pHLA。
Redirection of T lymphocytes toward cancer cells has been one of the most promising treatment concepts in oncology developed over the past years and leading to multiple regulatory approvals for both adoptive cell therapy (ACT) and T-cell-engaging bispecific (TEB) molecules. However, progress has been achieved predominantly in hematological indications by aiming at so-called lineage antigens (i.e. CD19, CD20, BCMA). Targeting of peptide-HLA antigens (pHLA) has been proposed as a strategy to overcome the paucity of suitable surface antigens in solid cancers, yet the technical hurdle to specifically address this class of low copy and highly promiscuous antigens has so far hampered its use in a broader patient population. We here describe the successful development of TCER (T-Cell-Engaging Receptor), a novel and highly versatile class of T-cell receptor (TCR)-based TEB with optimized in vivo efficacy, tolerability, plasma half-life, and stability characteristics for a broad use targeting pHLA in oncology and beyond.
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