CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.
CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.
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双特异性T细胞衔接器和CAR-T 在血液肿瘤中疗效显著。CD87在多种实体瘤中高表达并具有致癌作用。本研究评估其作为侵袭性无功能垂体腺瘤免疫治疗靶点的潜力。研究检测CD87表达及其对肿瘤细胞代谢的影响,并构建CD87特异性双特异性抗体及CAR/IL-12 T细胞。CD87在肿瘤组织和细胞中高表达,而非肿瘤脑组织未检出。CD87×CD3双特异性抗体及CD87 CAR/IL-12 T细胞均表现抗原特异性,可在体外抑制肿瘤细胞增殖,并在小鼠模型中缩小既有肿瘤。结果提示CD87是侵袭性无功能垂体腺瘤免疫治疗的潜在靶点。
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.
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