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抗体可变区工程改善癌症免疫治疗。

Antibody variable region engineering for improving cancer immunotherapy.

机构信息

Ludwig Institute of Cancer Research, University of Oxford, Oxford, OX3 7DR, UK.

Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.

出版信息

Cancer Commun (Lond). 2022 Sep;42(9):804-827. doi: 10.1002/cac2.12330. Epub 2022 Jul 13.

DOI:10.1002/cac2.12330
PMID:35822503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456695/
Abstract

The efficacy and specificity of conventional monoclonal antibody (mAb) drugs in the clinic require further improvement. Currently, the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention. Variable region-retaining antibody fragments, such as antigen-binding fragment (Fab), single-chain variable fragment (scFv), bispecific antibody, and bi/trispecific cell engagers, are engineered with humanization, multivalent antibody construction, affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody-based therapy potency, efficacy and specificity. In this review, we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies.

摘要

常规单克隆抗体 (mAb) 药物在临床上的疗效和特异性需要进一步提高。目前，新型抗体形式的开发和应用以改善癌症免疫疗法引起了广泛关注。保留可变区的抗体片段，如抗原结合片段 (Fab)、单链可变片段 (scFv)、双特异性抗体和双/三特异性细胞衔接子，通过人源化、多价抗体构建、亲和力优化和抗体掩蔽进行工程改造，以靶向肿瘤细胞和杀伤细胞，从而提高基于抗体的治疗效力、疗效和特异性。在本文中，我们总结了抗体可变区工程的应用，并讨论了改善癌症治疗的抗体工程的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a22c/9456695/feaa114105da/CAC2-42-804-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a22c/9456695/f64e244178fd/CAC2-42-804-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a22c/9456695/61bdcbd3a197/CAC2-42-804-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a22c/9456695/feaa114105da/CAC2-42-804-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a22c/9456695/f64e244178fd/CAC2-42-804-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a22c/9456695/61bdcbd3a197/CAC2-42-804-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a22c/9456695/feaa114105da/CAC2-42-804-g001.jpg

相似文献

[1]
Antibody variable region engineering for improving cancer immunotherapy.

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[2]
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[9]
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本文引用的文献

[1]
A general approach for stabilizing nanobodies for intracellular expression.

Elife. 2022-11-23

[2]
Antibody structure prediction using interpretable deep learning.

Patterns (N Y). 2021-12-9

[3]
Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer.

Oncoimmunology. 2022

[4]
Prodrug-Activating Chain Exchange (PACE) converts targeted prodrug derivatives to functional bi- or multispecific antibodies.

Biol Chem. 2022-4-26

[5]
CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia.

Leukemia. 2022-4

[6]
High efficacy and safety of CD38 and BCMA bispecific CAR-T in relapsed or refractory multiple myeloma.

J Exp Clin Cancer Res. 2022-1-3

[7]
Anti-SARS-CoV-1 and -2 nanobody engineering towards avidity-inspired therapeutics.

Nano Today. 2022-2

[8]
A novel anti-tumor/anti-tumor-associated fibroblast/anti-mPEG tri-specific antibody to maximize the efficacy of mPEGylated nanomedicines against fibroblast-rich solid tumor.

Biomater Sci. 2021-12-21

[9]
Engineering a cell-penetrating hyperstable antibody scFv(Ras) - An extraordinary approach to cancer therapeutics.

Synth Syst Biotechnol. 2021-10-20

[10]
Nanobody-Based Theranostic Agents for HER2-Positive Breast Cancer: Radiolabeling Strategies.

Int J Mol Sci. 2021-10-4

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