Abstract:
Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in iNFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.
摘要:
最近,双特异性T细胞衔接剂(BiTE)和嵌合抗原受体修饰的T细胞(CAR-Ts)已显示在血液肿瘤中具有高治疗功效。CD87在实体瘤中高表达,具有致癌功能。为了评估它们对侵袭性无功能垂体腺瘤(iNFPA)的细胞毒性作用,我们起首检测了CD87的表达及其对iNFPA细胞代谢的影响。我们产生了CD87特异性BiTE和CAR/IL-12T细胞,并确定了它们对iNFPAs细胞和小鼠模型的细胞毒性作用。CD87在iNFPA组织和细胞样品中高表达,但在非癌性脑样品中未检测到。CD87×CD3BiTE和CD87CAR/IL-12T细胞表现出抗原特异性,发挥了满意的细胞毒作用。降低体外肿瘤细胞增殖和减少实验小鼠中现有的肿瘤。总的来说,上述研究结果表明,CD87是使用抗CD87BiTE和CD87特异性CAR/IL-12T细胞对iNFPAs进行免疫治疗的有前景的靶标.