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长效白细胞介素-7 rhIL-7-hyFc 增强 CAR-T 细胞扩增、持久性与抗肿瘤活性

英文原题:A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity.

查看英文原题

A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity.

PubMed 2022/06/13(内容时间) Nat Commun Q1 · IF 18.1(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T 细胞疗法已常规用于治疗难治性血液系统恶性肿瘤患者。然而,相当比例患者的 CAR-T 细胞细胞毒性和持续存在能力不理想,可能导致肿瘤细胞逃逸和疾病复发。本研究显示,一种原型促淋巴细胞生长因子可增强 CAR-T 细胞疗效。研究证明,将长效重组人白细胞介素 7(IL-7)与杂合 Fc 融合形成的 rhIL-7-hyFc,可促进异种移植小鼠模型中人 CAR-T 细胞以及同系小鼠模型中小鼠 CAR-T 细胞的增殖、持续存在和细胞毒性,最终实现长期无瘤生存。因此,rhIL-7-hyFc 是一种可调节、可用于临床的辅助剂,有望改善 CAR-T 细胞活性不足的问题。

展开英文摘要原文

Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies.

However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse.

Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy.

We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival.

Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity.

论文信息

作者
Kim MY、Jayasinghe R、Devenport JM、Ritchey JK、Rettig MP、O'Neal J、Staser KW、Kennerly KM
第一作者单位
Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.United States
通讯作者单位
Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. jdipersi@wustl.edu.United States
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Nature communications2022 Jun 13
原文标识
PubMed 35697686 · DOI 10.1038/s41467-022-30860-0