PDF(Pubmed)
Abstract：
T-cell receptor (TCR) engineered T-cell therapy, unlike chimeric antigen receptor T-cell therapy, relies on the inherent ability of TCRs to detect a wider variety of antigenic epitopes, such as protein fragments found internally or externally on cells. Hence, TCR-T-cell therapy offers broader possibilities for treating solid tumors. However, because of the complicated process of identifying specific antigenic peptides, their clinical application still encounters significant challenges. Thus, we aimed to establish a novel \"universal\" TCR-T \"artificial antigen expression\" technique that involves the delivery of the antigen to tumor cells using DSPE-PEG-NY-ESO-1157-165 liposomes (NY-ESO-1 Lips) to express TCR-T-cell-specific recognition targets. In vitro as well as in vivo studies revealed that they could accumulate efficiently in the tumor area and deliver target antigens to activate the tumor-specific cytotoxic T-cell immune response. NY-ESO-1 TCR-T therapy, when used in combination, dramatically curbed tumor progression and extended the longevity of mice. Additionally, PD-1 blockage enhanced the therapeutic effect of the aforementioned therapy. In conclusion, NY-ESO-1 Lips \"cursed\" tumor cells by enabling antigenic target expression on their surface. This innovative technique presents a groundbreaking approach for the widespread utilization of TCR-T in solid tumor treatment.
摘要：
T细胞受体（TCR）工程T细胞治疗，与嵌合抗原受体T细胞疗法不同，依赖于TCR检测更广泛的抗原表位的固有能力，例如在细胞内部或外部发现的蛋白质片段。因此，TCR-T细胞疗法为治疗实体瘤提供了更广泛的可能性。然而,由于鉴定特定抗原肽的复杂过程，其临床应用仍面临重大挑战。因此，我们旨在建立一种新型的“通用”TCR-T“人工抗原表达”技术，该技术涉及使用DSPE-PEG-NY-ESO-1157-165脂质体（NY-ESO-1Lips）将抗原递送至肿瘤细胞，以表达TCR-T细胞特异性识别靶标。体外和体内研究表明，它们可以在肿瘤区域有效积累，并递送靶抗原以激活肿瘤特异性细胞毒性T细胞免疫反应。NY-ESO-1TCR-T疗法，当组合使用时，极大地抑制了肿瘤的进展，延长了小鼠的寿命。此外,PD-1阻断增强了上述疗法的治疗效果。总之,NY-ESO-1嘴唇通过使抗原靶标在其表面表达而“诅咒”肿瘤细胞。这种创新技术为TCR-T在实体瘤治疗中的广泛利用提供了开创性的方法。
