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抗 ErbB3 嵌合抗原受体 NK 细胞针对乳腺癌的治疗潜力

英文原题:Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer.

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Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer.

PubMed 2025/01/03(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

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中文摘要

ErbB3在乳腺癌细胞中显著过表达,并与耐药和转移相关。此外,ErbB3表达水平与TIL(肿瘤浸润淋巴细胞)密度较低呈正相关,而后者是预后不良的标志。因此,ErbB3是癌症免疫治疗的有前景靶点。本文报告了靶向ErbB3的嵌合抗原受体(CAR)改造自然杀伤(NK)细胞的制备:采用VSV-G包膜假型慢病毒载体转导脐带血来源原代NK细胞。转导后的细胞稳定表达CAR,对ErbB3阳性乳腺癌细胞系的细胞毒作用增强。此外,在SK-BR-3异种移植小鼠模型中,抗ErbB3(aErbB3)CAR-NK细胞显著降低肿瘤负荷,且未见明显副作用。这些发现凸显了aErbB3 CAR-NK细胞作为ErbB3阳性乳腺癌靶向免疫疗法的潜力,并提示其可能成为传统治疗的有前景替代方案。

展开英文摘要原文

ErbB3 is markedly overexpressed in breast cancer cells and is associated with resistance and metastasis.

Additionally, ErbB3 expression levels are positively correlated with low densities of tumor-infiltrating lymphocytes, a marker of poor prognosis. Consequently, ErbB3 is a promising therapeutic target for cancer immunotherapy.

Here, we report the generation of ErbB3-targeted chimeric antigen receptor (CAR)-modified natural killer (NK) cells by transducing cord blood-derived primary NK cells using vsv-g envelope-pseudotyped lentiviral vectors. Transduced cells displayed stable CAR-expressing activity and increased cytotoxicity against ErbB3-positive breast cancer cell lines.

Furthermore, anti-ErbB3 (aErbB3) CAR-NK cells strongly reduced the tumor burden in the SK-BR-3 xenograft mouse model without observable side effects.

These findings underscore the potential of aErbB3 CAR-NK cells as targeted immunotherapy for ErbB3-positive breast cancer, suggesting a promising alternative to conventional treatments.

论文信息

作者
Lee J、Song J、Yoo W、Choi H、Jung D、Choi E、Jo SG、Gong EY
第一作者单位
Department of Health Sciences, The Graduate School of Dong-A University, Busan, 49315, Republic of Korea.South Korea
通讯作者单位
Department of Health Sciences, The Graduate School of Dong-A University, Busan, 49315, Republic of Korea. cvaccine@dau.ac.kr.South Korea
期刊
Cancer immunology, immunotherapy : CII2025 Jan 3
原文标识
PubMed 39751931 · DOI 10.1007/s00262-024-03923-y