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:DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors.
DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors.
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本研究表明,DC 疫苗可促进 CAR-T 疗法在实体瘤中的效果,这为未来 CAR-T 细胞的广泛临床应用提供了可能。
CAR-T 细胞免疫疗法治疗血液系统肿瘤取得巨大成功,但治疗实体瘤尤其困难,因为 CAR-T 难以进入肿瘤内部并产生长期稳定的免疫效应。树突状细胞(DC)既可呈递肿瘤抗原,又可促进 T 细胞浸润。因此,借助 DC 疫苗增强 CAR-T 可能是治疗实体瘤的可靠策略。
为检验 DC 疫苗能否促进 CAR-T 治疗实体瘤,将 DC 疫苗与 MSLN CAR-T 细胞共培养,通过测量细胞增殖、分化和细胞因子分泌评估 DC 疫苗对 CAR-T 的体外作用。使用皮下荷瘤小鼠评估 DC 疫苗的体内作用,通过免疫荧光分析 CAR-T 浸润,并以实时定量 PCR 分析小鼠血液中 CAR-T 的持续存在。
DC 疫苗显著增强 MSLN CAR-T 细胞体外增殖潜力;不仅促进 CAR-T 细胞浸润,也显著提高其在体内实体瘤中的持续存在能力。
本研究证明 DC 疫苗可促进 CAR-T 治疗实体瘤,为未来 CAR-T 细胞的广泛临床应用提供了可能。
Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors.
To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR.
The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo.
In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future.
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