在选择 T 细胞受体进行治疗时需要考虑的免疫参数。
Immune parameters to consider when choosing T-cell receptors for therapy.
机构信息
Human Immunity Laboratory and Cellular Immunology Laboratory, Queensland Institute of Medical Research , Brisbane, QLD , Australia ; School of Medicine, The University of Queensland , Brisbane, QLD , Australia.
出版信息
Front Immunol. 2013 Aug 5;4:229. doi: 10.3389/fimmu.2013.00229. eCollection 2013.
Abstract
T-cell receptor (TCR) therapy has arrived as a realistic treatment option for many human diseases. TCR gene therapy allows for the mass redirection of T-cells against a defined antigen while high affinity TCR engineering allows for the creation of a new class of soluble drugs. However, deciding which TCR blueprint to take forward for gene therapy or engineering is difficult. More than one quintillion TCR combinations can be generated by somatic recombination and we are only now beginning to appreciate that not all are functionally equal. TCRs can exhibit high or low degrees of HLA-restricted cross-reactivity and alloreact against one or a combination of HLA alleles. Identifying TCR candidates with high specificity and minimal cross-reactivity/alloreactivity footprints before engineering is obviously highly desirable. Here we will summarize what we currently know about TCR biology with regard to immunoengineering.
摘要
T 细胞受体（TCR）治疗已经成为许多人类疾病的一种切实可行的治疗选择。TCR 基因治疗允许大量重定向 T 细胞针对特定抗原，而高亲和力 TCR 工程则允许创建一类新的可溶性药物。然而，决定采用哪种 TCR 蓝图进行基因治疗或工程是困难的。体细胞重组可以产生超过五千万亿种 TCR 组合，而我们现在才开始意识到并非所有 TCR 组合都是功能等同的。TCR 可以表现出高度或低度的 HLA 限制交叉反应性，并且针对一个或多个 HLA 等位基因发生同种异体反应。在工程设计之前，鉴定具有高特异性和最小交叉反应性/同种异体反应性足迹的 TCR 候选物显然是非常理想的。在这里，我们将总结目前我们所了解的 TCR 生物学与免疫工程学相关的内容。
相似文献
1
Immune parameters to consider when choosing T-cell receptors for therapy.在选择 T 细胞受体进行治疗时需要考虑的免疫参数。
Front Immunol. 2013 Aug 5;4:229. doi: 10.3389/fimmu.2013.00229. eCollection 2013.
2
Hepatitis E Virus (HEV)-Specific T Cell Receptor Cross-Recognition: Implications for Immunotherapy.戊型肝炎病毒（HEV）特异性 T 细胞受体交叉识别：免疫治疗的意义。
Front Immunol. 2019 Sep 4;10:2076. doi: 10.3389/fimmu.2019.02076. eCollection 2019.
3
Optimization of T-cell Reactivity by Exploiting TCR Chain Centricity for the Purpose of Safe and Effective Antitumor TCR Gene Therapy.利用 TCR 链的中心性优化 T 细胞反应性，以实现安全有效的抗肿瘤 TCR 基因治疗。
Cancer Immunol Res. 2015 Sep;3(9):1070-81. doi: 10.1158/2326-6066.CIR-14-0222. Epub 2015 May 5.
4
T-cell Receptors Engineered for Peptide Specificity Can Mediate Optimal T-cell Activity without Self Cross-Reactivity.经肽特异性工程改造的 T 细胞受体可以介导最佳 T 细胞活性而不具有自身交叉反应性。
Cancer Immunol Res. 2019 Dec;7(12):2025-2035. doi: 10.1158/2326-6066.CIR-19-0035. Epub 2019 Sep 23.
5
A rare population of tumor antigen-specific CD4CD8 double-positive αβ T lymphocytes uniquely provide CD8-independent TCR genes for engineering therapeutic T cells.一种罕见的肿瘤抗原特异性 CD4CD8 双阳性 αβ T 淋巴细胞群体，为工程化治疗性 T 细胞提供了独特的 CD8 非依赖性 TCR 基因。
J Immunother Cancer. 2019 Jan 9;7(1):7. doi: 10.1186/s40425-018-0467-y.
6
Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor histocompatibility antigen HA-2-specific T-cell receptor complexes expressing a conserved alpha joining region.利用表达保守α连接区的次要组织相容性抗原HA-2特异性T细胞受体复合物进行基因转移，重定向外周血T淋巴细胞的抗白血病反应性。
Blood. 2003 Nov 15;102(10):3530-40. doi: 10.1182/blood-2003-05-1524. Epub 2003 Jul 17.
7
Molecular docking analysis of 2009-H1N1 and 2004-H5N1 influenza virus HLA-B*4405-restricted HA epitope candidates: implications for TCR cross-recognition and vaccine development.2009-H1N1 和 2004-H5N1 流感病毒 HLA-B*4405 限制性 HA 表位候选物的分子对接分析：对 TCR 交叉识别和疫苗开发的意义。
BMC Bioinformatics. 2013;14 Suppl 2(Suppl 2):S21. doi: 10.1186/1471-2105-14-S2-S21. Epub 2013 Jan 21.
8
Chronic TCR-MHC (self)-interactions limit the functional potential of TCR affinity-increased CD8 T lymphocytes.慢性 TCR-MHC（自身）相互作用限制了 TCR 亲和力增加的 CD8 T 淋巴细胞的功能潜力。
J Immunother Cancer. 2019 Nov 5;7(1):284. doi: 10.1186/s40425-019-0773-z.
9
Preclinical Studies of the Off-Target Reactivity of AFP-Specific TCR Engineered T Cells.AFP 特异性 TCR 工程化 T 细胞的脱靶反应的临床前研究。
Front Immunol. 2020 Apr 27;11:607. doi: 10.3389/fimmu.2020.00607. eCollection 2020.
10
T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen.人类中针对病毒表位的T细胞受体库因对背景主要组织相容性复合体抗原的耐受性而多样化。
J Exp Med. 1995 Dec 1;182(6):1703-15. doi: 10.1084/jem.182.6.1703.
引用本文的文献
1
Stitchr: stitching coding TCR nucleotide sequences from V/J/CDR3 information.Stitchr：根据 V/J/CDR3 信息拼接编码 TCR 核苷酸序列。
Nucleic Acids Res. 2022 Jul 8;50(12):e68. doi: 10.1093/nar/gkac190.
2
Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential.具有治疗潜力的 HLA 限制性和人巨细胞病毒特异性抗体库的鉴定。
Cancer Immunol Immunother. 2020 Aug;69(8):1535-1548. doi: 10.1007/s00262-020-02564-1. Epub 2020 Apr 16.
3
TCR-like antibodies mediate complement and antibody-dependent cellular cytotoxicity against Epstein-Barr virus-transformed B lymphoblastoid cells expressing different HLA-A*02 microvariants.TCR 样抗体针对表达不同 HLA-A*02 微变异体的 Epstein-Barr 病毒转化的 B 淋巴母细胞系介导补体和抗体依赖性细胞细胞毒性作用。
Sci Rep. 2017 Aug 30;7(1):9923. doi: 10.1038/s41598-017-10265-6.
4
Understanding the complexity and malleability of T-cell recognition.理解T细胞识别的复杂性和可塑性。
Immunol Cell Biol. 2015 May-Jun;93(5):433-41. doi: 10.1038/icb.2014.112. Epub 2015 Jan 13.
5
Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection.分析急性乙型肝炎病毒感染康复者外周血淋巴细胞中T细胞受体β链可变基因库。
Cell Mol Immunol. 2014 Jul;11(4):332-42. doi: 10.1038/cmi.2014.22.
6
Bench, bedside, toolbox: T-cells deliver on every level.实验台、床边、工具箱：T细胞在各个层面都发挥着作用。
Front Immunol. 2014 Feb 3;5:31. doi: 10.3389/fimmu.2014.00031. eCollection 2014.
本文引用的文献
1
Single naive CD4+ T cells from a diverse repertoire produce different effector cell types during infection.在感染过程中，来自多样化 repertoire 的单个幼稚 CD4+ T 细胞可产生不同的效应细胞类型。
Cell. 2013 May 9;153(4):785-96. doi: 10.1016/j.cell.2013.04.007.
2
Highly divergent T-cell receptor binding modes underlie specific recognition of a bulged viral peptide bound to a human leukocyte antigen class I molecule.高度多样化的 T 细胞受体结合模式为特定识别与人类白细胞抗原 I 类分子结合的凸起病毒肽奠定了基础。
J Biol Chem. 2013 May 31;288(22):15442-54. doi: 10.1074/jbc.M112.447185. Epub 2013 Apr 8.
3
Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy.抗 MAGE-A3 TCR 基因治疗后的癌症消退和神经毒性。
J Immunother. 2013 Feb;36(2):133-51. doi: 10.1097/CJI.0b013e3182829903.
4
The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class I-like molecules.适应性强的主要组织相容性复合体（MHC）折叠结构：非经典和 MHC I 类样分子的结构与功能。
Annu Rev Immunol. 2013;31:529-61. doi: 10.1146/annurev-immunol-032712-095912. Epub 2013 Jan 7.
5
CD8+ TCR repertoire formation is guided primarily by the peptide component of the antigenic complex.CD8+ TCR repertoire 形成主要受抗原复合物中肽成分的指导。
J Immunol. 2013 Feb 1;190(3):931-9. doi: 10.4049/jimmunol.1202466. Epub 2012 Dec 24.
6
Peptide length determines the outcome of TCR/peptide-MHCI engagement.肽长度决定 TCR/肽-MHC I 结合的结果。
Blood. 2013 Feb 14;121(7):1112-23. doi: 10.1182/blood-2012-06-437202. Epub 2012 Dec 18.
7
Recognition of CD1d-restricted antigens by natural killer T cells.自然杀伤 T 细胞识别 CD1d 限制性抗原。
Nat Rev Immunol. 2012 Dec;12(12):845-57. doi: 10.1038/nri3328. Epub 2012 Nov 16.
8
High frequency of herpesvirus-specific clonotypes in the human T cell repertoire can remain stable over decades with minimal turnover.人类 T 细胞库中疱疹病毒特异性克隆型的高频可在数十年内保持稳定，几乎没有变化。
J Virol. 2013 Jan;87(1):697-700. doi: 10.1128/JVI.02180-12. Epub 2012 Oct 17.
9
MR1 presents microbial vitamin B metabolites to MAIT cells.MR1 将微生物维生素 B 代谢物呈递给 MAIT 细胞。
Nature. 2012 Nov 29;491(7426):717-23. doi: 10.1038/nature11605. Epub 2012 Oct 10.
10
A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons learned and much to be learned.从结构角度理解 MHC-I 限制性免疫应答：有教益，亦有更多待解。
Immunol Rev. 2012 Nov;250(1):61-81. doi: 10.1111/j.1600-065X.2012.01159.x.
Zotero 插件