A HER2-targeted CAR-T cell combined with IL-15 expression, a recombinant lentivirus expression plasmid and a preparation method and application thereof

By constructing a recombinant lentiviral vector expressing HER2-CAR and IL-15 and transducing CD3+ T cells, the problems of insufficient killing activity and poor in vivo persistence of HER2-targeted CAR-T cells in the treatment of solid tumors were solved. This achieved efficient killing and long-term survival of CAR-T cells, optimized their biological characteristics, and made them suitable for the treatment of HER2-positive breast cancer.

CN122405744APending Publication Date: 2026-07-17GUANGXI NORMAL UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
GUANGXI NORMAL UNIV
Filing Date
2026-06-03
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

HER2-targeting CAR-T cells have problems such as insufficient killing activity, poor persistence in vivo, and easy functional exhaustion in the treatment of solid tumors. There is an urgent need to construct efficient, stable, and safe HER2-targeting CAR-T cells that co-express IL-15 to optimize their function.

Method used

By constructing a recombinant lentiviral vector that can simultaneously express HER2-CAR and IL-15, CAR-T cells were transduced. The regulatory effect of IL-15 significantly enhanced in vitro killing activity, delayed cell exhaustion, and improved in vivo survival capacity. The preparation method included isolating CD3+ T cells, activating them, and transducing them with lentivirus to optimize the biological characteristics of CAR-T cells.

Benefits of technology

It significantly enhances the in vitro killing activity of CAR-T cells, prolongs their in vivo survival, optimizes their subset structure, reduces the expression of exhaustion markers, improves tumor suppression, and has good therapeutic safety, making it suitable for immunotherapy of solid tumors such as HER2-positive breast cancer.

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Abstract

本发明提供了一种联合表达IL‑15的靶向HER2的CAR‑T细胞、重组慢病毒表达质粒及其制备方法与应用,属于生物医药技术领域。本发明构建了可同时表达靶向HER2的嵌合抗原受体(CAR)和白细胞介素15(IL‑15)的慢病毒表达载体,其核苷酸序列如SEQ ID NO.7所示,将其转导至人外周血T细胞,获得联合表达IL‑15的靶向HER2的CAR‑T细胞。该细胞可特异性识别并杀伤HER2阳性肿瘤细胞;IL‑15共表达能显著增强体外杀伤活性、促进效应T细胞增殖、提升毒性因子分泌水平,同时延缓T细胞耗竭、改善线粒体功能,提高体内存续与抑瘤效果,且安全性良好、无明显脱靶毒性及肝损伤,为HER2阳性乳腺癌等实体瘤免疫治疗提供高效安全新策略,具有重要临床转化价值。
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