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:Armed with IL-2 based fusion protein improves CAR-T cell fitness and efficacy against solid tumors.
Armed with IL-2 based fusion protein improves CAR-T cell fitness and efficacy against solid tumors.
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CAR-T(CAR-T)细胞疗法是一种强效免疫疗法,通过诱导抗原特异性免疫应答,已在血液系统恶性肿瘤治疗中取得重大成功。然而,对于具有免疫抑制性微环境的实体瘤,CAR-T 细胞疗法缓解率仍有限。联合工程化策略正推动相关方法发展,以克服免疫抑制屏障并增强抗肿瘤应答。本研究构建了一种共工程化IL-2突变体CAR-T 细胞,以增强CAR-T 细胞对抗实体瘤的能力并有效抑制肿瘤。我们使CAR-T 细胞同时表达靶向肿瘤抗原的CAR和突变型人白细胞介素2(IL-2m),从而增强CAR-T 细胞体外适应性、重塑免疫排斥型肿瘤微环境、提高CAR-T 细胞在实体瘤中的浸润,并改善肿瘤控制,且未见显著全身毒性。总体而言,本研究展示了一种通用的CAR-T 细胞武装策略,可用于开发和优化对抗实体瘤的CAR-T 细胞。
Chimeric antigen receptor T (CAR-T) cell therapy is regarded as a potent immunotherapy and has made significant success in hematologic malignancies by eliciting antigen-specific immune responses.
However, response rates of CAR-T cell therapy against solid tumors with immunosuppressive microenvironments remain limited. Co-engineering strategies are advancing methods to overcome immunosuppressive barriers and enhance antitumor responses.
Here, we engineered an IL-2 mutein co-engineered CAR-T for the improvement of CAR-T cells against solid tumors and the efficient inhibition of solid tumors.
We equipped the CAR-T cells with co-expressing both tumor antigen-targeted CAR and a mutated human interleukin-2 (IL-2m), conferring enhanced CAR-T cells fitness in vitro, reshaped immune-excluded TME, enhanced CAR-T infiltration in solid tumors, and improved tumor control without significant systemic toxicity.
Overall, this subject demonstrates the universal CAR-T cells armed strategy for the development and optimization of CAR-T cells against solid tumors.
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