Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Nuclear Medicine and PET Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Immunol. 2021 Mar 29;12:652924. doi: 10.3389/fimmu.2021.652924. eCollection 2021.
As many patients ultimately relapse after chimeric antigen receptor (CAR) T-cell therapy, identification of alternative targets is currently being evaluated. Substantial research efforts are underway to develop new targets. The transferrin receptor (TfR) is prevalently expressed on rapidly proliferating tumor cells and holds the potential to be the alternative target. In order to investigate the efficacy and challenges of TfR-targeting on the CAR-based therapy strategy, we generated a TfR-specific CAR and established the TfR-CAR-modified T cells. To take the advantage of TfR being widely shared by multiple tumors, TfR-CAR T cells were assessed against several TfR hematological malignant cell lines. Data showed that TfR-CAR T cells were powerfully potent in killing all these types of cells and in killing T-ALL cells . These findings suggest that TfR could be a universal target to broaden and improve the therapeutic efficacy of CAR T cells and warrant further efforts to use these cells as an alternative CAR T cell product for the therapy of hematological malignancies.
由于许多患者在嵌合抗原受体 (CAR) T 细胞治疗后最终会复发，因此目前正在评估替代靶标的识别。正在进行大量的研究工作来开发新的靶标。转铁蛋白受体 (TfR) 在快速增殖的肿瘤细胞上普遍表达，具有成为替代靶标的潜力。为了研究 TfR 靶向在基于 CAR 的治疗策略中的疗效和挑战，我们生成了 TfR 特异性 CAR，并建立了 TfR-CAR 修饰的 T 细胞。为了利用 TfR 被多种肿瘤广泛共享的优势，我们评估了 TfR-CAR T 细胞对几种 TfR 血液恶性细胞系的作用。数据表明，TfR-CAR T 细胞能够强力杀伤所有这些类型的细胞，包括 T-ALL 细胞。这些发现表明 TfR 可以成为拓宽和提高 CAR T 细胞治疗效果的通用靶标，并值得进一步努力将这些细胞用作血液恶性肿瘤治疗的替代 CAR T 细胞产品。
