The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
Cell Immunol. 2021 Jul;365:104376. doi: 10.1016/j.cellimm.2021.104376. Epub 2021 May 5.
Adoptive T cell transfer is one of the most promising ways to combat solid tumors. However, the weak infiltration of T cells into tumor sites has restricted their antitumor efficacy. To overcome this obstacle, we used the lipophilic protein painting strategy to improve tumor targeting and penetrating capacity of lymphocytes for the first time. We synthesized the lipid anchor consisting of a bispecific recombinant protein iRGD-antiEGFR and DSPE-PEG derivates, then successfully inserted it into the membranes of T cells. This surface modification was non-invasive and could efficiently improve the infiltration ability of T cells into multicellular spheroids and tumor masses. The surface modified T cells also displayed superior antitumor activities in EGFR-positive tumor xenografts via systematic infusion. Moreover, the permeability and antitumor efficacy of these surface painted T cells could be remarkably enhanced when used in combination with local low-dose irradiation.
过继性 T 细胞转移是治疗实体瘤最有前途的方法之一。然而，T 细胞在肿瘤部位的浸润较弱限制了其抗肿瘤效果。为了克服这一障碍，我们首次使用亲脂性蛋白涂覆策略来提高淋巴细胞对肿瘤的靶向性和穿透能力。我们合成了由双特异性重组蛋白 iRGD-antiEGFR 和 DSPE-PEG 衍生物组成的脂质锚，然后成功地将其插入 T 细胞的膜中。这种表面修饰是非侵入性的，可有效提高 T 细胞在多细胞球体和肿瘤块中的浸润能力。通过系统输注，表面修饰的 T 细胞在 EGFR 阳性肿瘤异种移植物中也显示出优异的抗肿瘤活性。此外，当与局部低剂量照射联合使用时，这些表面涂覆的 T 细胞的通透性和抗肿瘤效果可以显著增强。
