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开发靶向EphA2的嵌合抗原受体T细胞/自然杀伤细胞用于非小细胞肺癌治疗。

Developing CAR-T/NK cells that target EphA2 for non-small cell lung cancer treatment.

作者信息

Kim Seok Min, Lee Soo Yun, Kim Seo In, Bae Ji Yeong, Hong Jin Tae, Jo Seona, Kim Ji Hyun, Chung Hyo-Young, Kim Tae-Don

机构信息

Center for Gene & Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.

New Drug Development Center, Osong Medical Innovation Foundation, Cheongju-si, Chungbuk, Republic of Korea.

出版信息

Front Immunol. 2025 Mar 13;16:1448438. doi: 10.3389/fimmu.2025.1448438. eCollection 2025.

DOI:10.3389/fimmu.2025.1448438
PMID:40181964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11966065/
Abstract

INTRODUCTION

Chimeric antigen receptor (CAR) immunotherapy has revolutionized anticancer therapy, as it accurately targets cancer cells by recognizing specific antigens expressed in cancer cells. This innovative therapeutic strategy has attracted considerable attention. However, few therapeutics are available for treating non-small cell lung cancer (NSCLC), which accounts for most lung cancer cases and is one of the deadliest cancers with low survival rates.

METHODS

In this study, we developed a new antibody targeting erythropoietin-producing hepatocellular carcinoma A2 (EphA2), which is highly expressed in NSCLC, and established CAR-T/ natural killer (NK) immune cells to verify its potential for immune cell therapy. The killing capacity, cytokine secretion and solid tumor growth inhibition of EphA2 CAR-T/NK cells were compared to normal T/NK cells.

RESULTS

EphA2 CAR-T cells demonstrated superior killing capacity, enhanced cytokine secretion, and significant solid tumor growth inhibition. Additionally, they exhibited improved tumor infiltration in lung cancer models compared to normal T cells. The anticancer efficacy of the developed EphA2 CAR-NK cells was also confirmed, showcasing their potential as robust candidates for immune cell therapy.

DISCUSSION

The findings of this study highlight the potential of CAR-T/NK cell therapy targeting EphA2 as an effective treatment for lung cancer, particularly NSCLC with high EphA2 expression. By leveraging the specific targeting capabilities of CAR-T cells and the unique properties of CAR-NK cells, this approach provides a promising therapeutic strategy to address the unmet needs in NSCLC treatment.

摘要

引言

嵌合抗原受体(CAR)免疫疗法彻底改变了抗癌治疗方式,因为它通过识别癌细胞中表达的特定抗原精确靶向癌细胞。这种创新的治疗策略已引起广泛关注。然而,可用于治疗非小细胞肺癌(NSCLC)的疗法很少,NSCLC占大多数肺癌病例,是最致命的癌症之一,生存率很低。

方法

在本研究中,我们开发了一种靶向促红细胞生成素产生肝细胞癌A2(EphA2)的新型抗体,EphA2在NSCLC中高表达,并建立了CAR-T/自然杀伤(NK)免疫细胞以验证其免疫细胞治疗潜力。将EphA2 CAR-T/NK细胞的杀伤能力、细胞因子分泌和实体瘤生长抑制与正常T/NK细胞进行比较。

结果

EphA2 CAR-T细胞表现出卓越的杀伤能力、增强的细胞因子分泌和显著的实体瘤生长抑制。此外,与正常T细胞相比,它们在肺癌模型中表现出更好的肿瘤浸润。所开发的EphA2 CAR-NK细胞的抗癌疗效也得到证实,显示出它们作为免疫细胞治疗有力候选者的潜力。

讨论

本研究结果突出了靶向EphA2的CAR-T/NK细胞疗法作为肺癌尤其是高表达EphA2的NSCLC有效治疗方法的潜力。通过利用CAR-T细胞的特异性靶向能力和CAR-NK细胞的独特特性,这种方法为满足NSCLC治疗中未满足的需求提供了一种有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/383fb321410a/fimmu-16-1448438-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/da015f082379/fimmu-16-1448438-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/383fb321410a/fimmu-16-1448438-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/ad7edd684ca0/fimmu-16-1448438-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/7d1935485e0a/fimmu-16-1448438-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/d634353fe204/fimmu-16-1448438-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/da015f082379/fimmu-16-1448438-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57e/11966065/383fb321410a/fimmu-16-1448438-g007.jpg

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CAR-NK Cells: A Chimeric Hope or a Promising Therapy?嵌合抗原受体自然杀伤细胞(CAR-NK细胞):是一种虚幻的希望还是一种有前景的疗法?
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Natural killer cells in antitumour adoptive cell immunotherapy.肿瘤过继细胞免疫治疗中的自然杀伤细胞
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