Zarei Mahdi, Abdoli Shahriyar, Farazmandfar Touraj, Shahbazi Majid
Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Heliyon. 2023 Sep 27;9(10):e20460. doi: 10.1016/j.heliyon.2023.e20460. eCollection 2023 Oct.
Although CAR-based immunotherapy is viewed as a promising treatment for tumors, particularly hematological malignancies, solid tumors can pose challenges. It has been suggested that the immunomodulatory medication Lenalidomide (LEN) may increase the effectiveness of CAR T cells in the treatment of solid tumors. The purpose of our study was to investigate the effect of NKG2D-based CAR T cell therapy on colorectal cancer cell lines, and then we assessed combinatorial therapy using NKG2D CAR T cells and lenalidomide in vitro.
To prepare NKG2D CAR T cells, a second-generation NKG2D-CAR construct was designed and transfected into the T cells using a lentiviral system. The NKG2D CAR T cells showed significantly higher cytotoxic activity against colorectal cancer cell lines, HCT116 and SW480, compared to untransduced T cells. In addition, our data demonstrated that the cytotoxicity and cytokine secretion of NKG2D CAR T cells significantly increased in the presence of higher doses of lenalidomide.
The study findings suggest that combinational therapy, utilizing NKG2D-based CAR T cells and lenalidomide, has a high potential for effectively eliminating tumor cells in vitro.
尽管基于嵌合抗原受体（CAR）的免疫疗法被视为治疗肿瘤，尤其是血液系统恶性肿瘤的一种有前景的治疗方法，但实体瘤可能带来挑战。有人提出免疫调节药物来那度胺（LEN）可能会提高CAR T细胞治疗实体瘤的有效性。我们研究的目的是调查基于自然杀伤细胞2D（NKG2D）的CAR T细胞疗法对结肠癌细胞系的影响，然后我们在体外评估了使用NKG2D CAR T细胞和来那度胺的联合疗法。
为制备NKG2D CAR T细胞，设计了第二代NKG2D - CAR构建体，并使用慢病毒系统将其转染到T细胞中。与未转导的T细胞相比，NKG2D CAR T细胞对结肠癌细胞系HCT116和SW480显示出显著更高的细胞毒性活性。此外，我们的数据表明，在较高剂量来那度胺存在的情况下，NKG2D CAR T细胞的细胞毒性和细胞因子分泌显著增加。
研究结果表明，利用基于NKG2D的CAR T细胞和来那度胺的联合疗法在体外有效消除肿瘤细胞具有很大潜力。
