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基于T细胞的癌症免疫疗法:方法与策略

T Cell Based Immunotherapy for Cancer: Approaches and Strategies.

作者信息

Want Muzamil Y, Bashir Zeenat, Najar Rauf A

机构信息

Department of Immunology, Division of Translational Immuno-Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Department of Chemistry and Biochemistry, Canisius College, Buffalo, NY 14208, USA.

出版信息

Vaccines (Basel). 2023 Apr 13;11(4):835. doi: 10.3390/vaccines11040835.


DOI:10.3390/vaccines11040835
PMID:37112747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10142387/
Abstract

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progress has been made in T cell-based immunotherapy over the past decade, using naturally occurring or genetically engineered T cells to target cancer antigens in hematological malignancies and solid tumors. However, limited specificity, longevity, and toxicity have limited success rates. This review provides an overview of T cells as a therapeutic tool for cancer, highlighting the advantages and future strategies for developing effective T cell cancer immunotherapy. The challenges associated with identifying T cells and their corresponding antigens, such as their low frequency, are also discussed. The review further examines the current state of T cell-based immunotherapy and potential future strategies, such as the use of combination therapy and the optimization of T cell properties, to overcome current limitations and improve clinical outcomes.

摘要

T细胞通过识别癌细胞或抗原呈递细胞上由MHC分子呈递的抗原,在破坏癌细胞方面起着关键作用。识别并靶向癌症特异性或过度表达的自身抗原对于重定向T细胞对抗肿瘤至关重要,从而导致肿瘤消退。这是通过识别癌细胞中突变或过度表达的自身蛋白来实现的,这些蛋白指导T细胞受体对癌细胞的识别。基于T细胞的免疫疗法主要有两种方法:HLA限制性和HLA非限制性免疫疗法。在过去十年中,基于T细胞的免疫疗法取得了重大进展,使用天然存在的或基因工程改造的T细胞来靶向血液系统恶性肿瘤和实体瘤中的癌症抗原。然而,有限的特异性、寿命和毒性限制了成功率。本综述概述了T细胞作为癌症治疗工具的情况,强调了开发有效的T细胞癌症免疫疗法的优势和未来策略。还讨论了与识别T细胞及其相应抗原相关的挑战,例如它们的低频率。该综述进一步研究了基于T细胞的免疫疗法的现状以及潜在的未来策略,例如使用联合疗法和优化T细胞特性,以克服当前的局限性并改善临床结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ea4/10142387/f3dd708226f9/vaccines-11-00835-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ea4/10142387/f3dd708226f9/vaccines-11-00835-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ea4/10142387/f3dd708226f9/vaccines-11-00835-g001.jpg

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T Cell Based Immunotherapy for Cancer: Approaches and Strategies.

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[6]
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[7]
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[9]
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[10]
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本文引用的文献

[1]
Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment.

Cancers (Basel). 2023-1-17

[2]
γδ T cells are effectors of immunotherapy in cancers with HLA class I defects.

Nature. 2023-1

[3]
Engineering Human MAIT Cells with Chimeric Antigen Receptors for Cancer Immunotherapy.

J Immunol. 2022-10-15

[4]
Quantitative immunopeptidomics reveals a tumor stroma-specific target for T cell therapy.

Sci Transl Med. 2022-8-31

[5]
CAR γδ T cells for cancer immunotherapy. Is the field more yellow than green?

Cancer Immunol Immunother. 2023-2

[6]
Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor-Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors.

Cancer Immunol Res. 2022-8-3

[7]
Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy.

Cancers (Basel). 2022-6-18

[8]
Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer.

N Engl J Med. 2022-6-2

[9]
Development of Highly Effective Anti-Mesothelin hYP218 Chimeric Antigen Receptor T Cells With Increased Tumor Infiltration and Persistence for Treating Solid Tumors.

Mol Cancer Ther. 2022-7-5

[10]
Innovative Strategies to Improve the Clinical Application of NK Cell-Based Immunotherapy.

Front Immunol. 2022

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