Tîrziu Alexandru, Gavriliuc Oana-Isabella, Bojin Maria-Florina, Păunescu Virgil
Department of Functional Sciences, Immuno-Physiology and Biotechnologies Center, "Victor Babes" University of Medicine and Pharmacy, No. 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
Center for Gene and Cellular Therapies in the Treatment of Cancer Timisoara-OncoGen, Clinical Emergency County Hospital "Pius Brinzeu" Timisoara, No. 156 Liviu Rebreanu, 300723 Timisoara, Romania.
Biomedicines. 2025 Jan 22;13(2):264. doi: 10.3390/biomedicines13020264.
Chimeric antigen receptor (CAR) T cell therapy has shown significant promise in treating hematological malignancies, yet its application in solid tumors, particularly those expressing the epidermal growth factor receptor (EGFR), remains limited. This study investigates the potential of CAR-engineered peripheral blood mononuclear cells (PBMCs) as a novel adoptive cell therapy against EGFR-positive cancers. Lentiviral transduction at an MOI of 50 was performed to generate specific anti-EGFR second generation CAR-effector cells. The transduced PBMCs were stimulated with cytokines and CD3/CD28 beads to enhance their proliferation and activation. Flow cytometric and real-time cell analysis were performed at various effector-to-target ratios to explore the cytotoxic potential of CAR-PBMCs. CAR-PBMCs exhibited improved targeting and cytotoxicity against EGFR-positive cancer cell lines MDA-MB-468 and SK-BR-3, compared to untransduced controls, with unsignificant effects on allogeneic PBMCs. CAR-PBMCs hold considerable potential as a therapeutic strategy for EGFR-positive solid tumors, warranting further clinical investigation.
嵌合抗原受体(CAR)T细胞疗法在治疗血液系统恶性肿瘤方面已显示出巨大潜力,但其在实体瘤,尤其是表达表皮生长因子受体(EGFR)的实体瘤中的应用仍然有限。本研究调查了经CAR工程改造的外周血单个核细胞(PBMC)作为一种针对EGFR阳性癌症的新型过继性细胞疗法的潜力。以50的感染复数进行慢病毒转导,以产生特异性抗EGFR第二代CAR效应细胞。用细胞因子和CD3/CD28磁珠刺激转导后的PBMC,以增强其增殖和活化。在不同的效应细胞与靶细胞比例下进行流式细胞术和实时细胞分析,以探索CAR-PBMC的细胞毒性潜力。与未转导的对照相比,CAR-PBMC对EGFR阳性癌细胞系MDA-MB-468和SK-BR-3表现出更好的靶向性和细胞毒性,对同种异体PBMC无显著影响。CAR-PBMC作为EGFR阳性实体瘤的一种治疗策略具有相当大的潜力,值得进一步的临床研究。