文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

优化 CAR-T 细胞疗法治疗实体瘤:当前挑战与潜在策略。

Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.

机构信息

Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, Guangdong, China.

Department of Hematology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Er Road, Guangzhou, 510280, Guangdong, China.

出版信息

J Hematol Oncol. 2024 Nov 5;17(1):105. doi: 10.1186/s13045-024-01625-7.


DOI:10.1186/s13045-024-01625-7
PMID:39501358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11539560/
Abstract

Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application in solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T cells. Despite improvements from fourth and next-generation CAR-T cells, new challenges include systemic toxicity from continuously secreted proteins, low productivity, and elevated costs. Recent research targets genetic modifications to boost killing potential, metabolic interventions to hinder tumor progression, and diverse combination strategies to enhance CAR-T cell therapy. Efforts to reduce the duration and cost of CAR-T cell therapy include developing allogenic and in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies and platforms enhance the potential of CAR-T cell therapy to overcome limitations in treating solid tumors. This review explores strategies to optimize CAR-T cell therapies for solid tumors, focusing on enhancing cytotoxicity and overcoming application restrictions. We summarize recent advances in T cell subset selection, CAR-T structural modifications, infiltration enhancement, genetic and metabolic interventions, production optimization, and the integration of novel technologies, presenting therapeutic approaches that could improve CAR-T cell therapy's efficacy and applicability in solid tumors.

摘要

嵌合抗原受体 (CAR)-T 细胞疗法在各种血液恶性肿瘤中显示出显著的疗效。然而,其在实体瘤中的应用仍然有限。临床研究报告了不理想的结果,例如 CAR-T 细胞的细胞毒性降低和肿瘤逃逸,这凸显了需要解决 CAR-T 细胞滑动细胞毒性的挑战。尽管第四代和下一代 CAR-T 细胞有所改进,但新的挑战包括连续分泌蛋白的全身毒性、低生产率和成本升高。最近的研究目标是通过基因修饰来提高杀伤潜力、代谢干预来阻碍肿瘤进展以及采用多种组合策略来增强 CAR-T 细胞疗法。减少 CAR-T 细胞疗法的持续时间和成本的努力包括开发同种异体和体内方法,有望取得重大的未来进展。同时,创新技术和平台增强了 CAR-T 细胞疗法治疗实体瘤的潜力,克服了其在治疗实体瘤方面的限制。本综述探讨了优化 CAR-T 细胞疗法治疗实体瘤的策略,重点是增强细胞毒性和克服应用限制。我们总结了 T 细胞亚群选择、CAR-T 结构修饰、浸润增强、遗传和代谢干预、生产优化以及新型技术整合方面的最新进展,提出了可能提高 CAR-T 细胞疗法在实体瘤中的疗效和适用性的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/941e6b7c1fbd/13045_2024_1625_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/7569b1a76447/13045_2024_1625_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/c3f53a82e21b/13045_2024_1625_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/0f253bbdb994/13045_2024_1625_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/d518e6031e67/13045_2024_1625_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/66bd31733cf0/13045_2024_1625_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/16af856a9875/13045_2024_1625_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/6795bff3f80b/13045_2024_1625_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/941e6b7c1fbd/13045_2024_1625_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/7569b1a76447/13045_2024_1625_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/c3f53a82e21b/13045_2024_1625_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/0f253bbdb994/13045_2024_1625_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/d518e6031e67/13045_2024_1625_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/66bd31733cf0/13045_2024_1625_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/16af856a9875/13045_2024_1625_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/6795bff3f80b/13045_2024_1625_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/11539560/941e6b7c1fbd/13045_2024_1625_Fig8_HTML.jpg

相似文献

[1]
Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.

J Hematol Oncol. 2024-11-5

[2]
Advanced Strategies of CAR-T Cell Therapy in Solid Tumors and Hematological Malignancies.

Recent Pat Anticancer Drug Discov. 2024

[3]
CAR-T therapy in solid tumors.

Cancer Cell. 2025-4-14

[4]
Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.

Front Immunol. 2025-1-6

[5]
Chimeric Antigen Receptor Cells Solid Tumor Immunotherapy Assisted by Biomaterials Tools.

ACS Appl Mater Interfaces. 2025-2-19

[6]
Nanomaterials Boost CAR-T Therapy for Solid Tumors.

Adv Healthc Mater. 2024-8

[7]
CAR-T therapy dilemma and innovative design strategies for next generation.

Cell Death Dis. 2025-3-27

[8]
Revolutionizing CAR T-Cell Therapies: Innovations in Genetic Engineering and Manufacturing to Enhance Efficacy and Accessibility.

Int J Mol Sci. 2024-9-26

[9]
Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.

Front Immunol. 2018-7-31

[10]
CAR-T cell therapy: current limitations and potential strategies.

Blood Cancer J. 2021-4-6

引用本文的文献

[1]
Can We Use CAR-T Cells to Overcome Immunosuppression in Solid Tumours?

Biology (Basel). 2025-8-12

[2]
Recent advances in universal chimeric antigen receptor T cell therapy.

J Hematol Oncol. 2025-8-29

[3]
Challenges in the preclinical design and assessment of CAR-T cells.

Front Immunol. 2025-8-8

[4]
hCCL19-expressing recombinant Newcastle disease virus boosts CAR T cell infiltration and efficacy in solid tumor.

J Immunother Cancer. 2025-7-25

[5]
Unraveling the Complex Cellular Repair Mechanisms Following Myocardial Infarction.

Int J Mol Sci. 2025-6-23

[6]
CAR-T cell therapy for cancer: current challenges and future directions.

Signal Transduct Target Ther. 2025-7-4

[7]
Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.

Exp Hematol Oncol. 2025-7-2

[8]
Advancing liver cancer treatment with dual-targeting CAR-T therapy.

J Nanobiotechnology. 2025-6-24

[9]
Beyond Exosomes: An Ultrapurified Phospholipoproteic Complex (PLPC) as a Scalable Immunomodulatory Platform for Reprogramming Immune Suppression in Metastatic Cancer.

Cancers (Basel). 2025-5-14

[10]
Tumor microenvironment and immune-related myositis: addressing muscle wasting in cancer immunotherapy.

Front Immunol. 2025-5-2

本文引用的文献

[1]
Lipid-based nanosystems: the next generation of cancer immune therapy.

J Hematol Oncol. 2024-7-19

[2]
Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy.

J Hematol Oncol. 2024-6-11

[3]
CRISPR/Cas-based CAR-T cells: production and application.

Biomark Res. 2024-5-31

[4]
Advances in nano-immunotherapy for hematological malignancies.

Exp Hematol Oncol. 2024-5-25

[5]
Mapping variant effects on anti-tumor hallmarks of primary human T cells with base-editing screens.

Nat Biotechnol. 2025-3

[6]
Critical role of the gut microbiota in immune responses and cancer immunotherapy.

J Hematol Oncol. 2024-5-14

[7]
TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors.

Sci Adv. 2024-5-10

[8]
The dilemmas and possible solutions for CAR-T cell therapy application in solid tumors.

Cancer Lett. 2024-6-1

[9]
FOXO1 is a master regulator of memory programming in CAR T cells.

Nature. 2024-5

[10]
FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy.

Nature. 2024-5

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索