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使用生物发光成像评估人源化小鼠模型中人类嵌合抗原受体自然杀伤细胞(CAR-NKT细胞)药代动力学和药效学的方案。

Protocol for assessing pharmacokinetics and pharmacodynamics of human CAR-NKT cells in humanized mouse models using bioluminescence imaging.

作者信息

Lyu Zibai, Li Yan-Ruide, Yang Lili

机构信息

Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

STAR Protoc. 2025 Jul 19;6(3):103957. doi: 10.1016/j.xpro.2025.103957.

Abstract

Human invariant natural killer T (NKT) cells exhibit strong tumor-killing ability and bridge innate and adaptive immunity. Peripheral blood mononuclear cell (PBMC)-derived chimeric antigen receptor (CAR)-engineered NKT (CAR-NKT) cells show potent anti-tumor activity. Here, we present a protocol for assessing the pharmacokinetics and pharmacodynamics (PK/PD) of PBMC-derived CAR-NKT cells in humanized mouse models using in vivo bioluminescence imaging (BLI). We describe steps for evaluating CAR-NKT cell distribution, persistence, and tumor infiltration across tumor-free and tumor-bearing models to support CAR-NKT cell therapy development. For complete details on the use and execution of this protocol, please refer to Li et al..

摘要

人类不变自然杀伤T(NKT)细胞具有强大的肿瘤杀伤能力,并在固有免疫和适应性免疫之间起桥梁作用。外周血单个核细胞(PBMC)来源的嵌合抗原受体(CAR)工程化NKT(CAR-NKT)细胞表现出强大的抗肿瘤活性。在此,我们展示了一种使用体内生物发光成像(BLI)在人源化小鼠模型中评估PBMC来源的CAR-NKT细胞药代动力学和药效学(PK/PD)的方案。我们描述了评估CAR-NKT细胞在无肿瘤和有肿瘤模型中的分布、持久性和肿瘤浸润的步骤,以支持CAR-NKT细胞疗法的开发。有关本方案使用和执行的完整详细信息,请参考Li等人的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/12302916/4687f79e022d/fx1.jpg

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