vNARs as Neutralizing Intracellular Therapeutic Agents: Glioblastoma as a Target

IF 3 Q3 IMMUNOLOGY

Antibodies Pub Date : 2024-03-18 DOI:10.3390/antib13010025

Alejandro Manzanares-Guzmán, P. H. Lugo-Fabres, T. Camacho-Villegas

{"title":"vNARs as Neutralizing Intracellular Therapeutic Agents: Glioblastoma as a Target","authors":"Alejandro Manzanares-Guzmán, P. H. Lugo-Fabres, T. Camacho-Villegas","doi":"10.3390/antib13010025","DOIUrl":null,"url":null,"abstract":"Glioblastoma is the most prevalent and fatal form of primary brain tumors. New targeted therapeutic strategies for this type of tumor are imperative given the dire prognosis for glioblastoma patients and the poor results of current multimodal therapy. Previously reported drawbacks of antibody-based therapeutics include the inability to translocate across the blood–brain barrier and reach intracellular targets due to their molecular weight. These disadvantages translate into poor target neutralization and cancer maintenance. Unlike conventional antibodies, vNARs can permeate tissues and recognize conformational or cryptic epitopes due to their stability, CDR3 amino acid sequence, and smaller molecular weight. Thus, vNARs represent a potential antibody format to use as intrabodies or soluble immunocarriers. This review comprehensively summarizes key intracellular pathways in glioblastoma cells that induce proliferation, progression, and cancer survival to determine a new potential targeted glioblastoma therapy based on previously reported vNARs. The results seek to support the next application of vNARs as single-domain antibody drug-conjugated therapies, which could overcome the disadvantages of conventional monoclonal antibodies and provide an innovative approach for glioblastoma treatment.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antibodies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/antib13010025","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Glioblastoma is the most prevalent and fatal form of primary brain tumors. New targeted therapeutic strategies for this type of tumor are imperative given the dire prognosis for glioblastoma patients and the poor results of current multimodal therapy. Previously reported drawbacks of antibody-based therapeutics include the inability to translocate across the blood–brain barrier and reach intracellular targets due to their molecular weight. These disadvantages translate into poor target neutralization and cancer maintenance. Unlike conventional antibodies, vNARs can permeate tissues and recognize conformational or cryptic epitopes due to their stability, CDR3 amino acid sequence, and smaller molecular weight. Thus, vNARs represent a potential antibody format to use as intrabodies or soluble immunocarriers. This review comprehensively summarizes key intracellular pathways in glioblastoma cells that induce proliferation, progression, and cancer survival to determine a new potential targeted glioblastoma therapy based on previously reported vNARs. The results seek to support the next application of vNARs as single-domain antibody drug-conjugated therapies, which could overcome the disadvantages of conventional monoclonal antibodies and provide an innovative approach for glioblastoma treatment.

查看原文本刊更多论文

vNARs 作为中和细胞内治疗药物：以胶质母细胞瘤为靶点

胶质母细胞瘤是最常见、最致命的原发性脑肿瘤。鉴于胶质母细胞瘤患者的预后很差，而目前的多模式疗法效果不佳，因此针对这类肿瘤的新靶向治疗策略势在必行。以前报道过的抗体疗法的缺点包括：由于分子量的原因，抗体无法穿过血脑屏障到达细胞内靶点。这些缺点导致靶点中和和癌症维持能力差。与传统抗体不同，vNARs 由于其稳定性、CDR3 氨基酸序列和较小的分子量，可以渗透组织并识别构象表位或隐匿表位。因此，vNARs 是一种可用作体内抗体或可溶性免疫载体的潜在抗体形式。本综述全面总结了胶质母细胞瘤细胞中诱导增殖、进展和癌症存活的关键细胞内通路，以确定基于先前报道的 vNARs 的新的潜在胶质母细胞瘤靶向疗法。研究结果旨在支持 vNARs 作为单域抗体药物结合疗法的下一步应用，它可以克服传统单克隆抗体的缺点，为胶质母细胞瘤治疗提供一种创新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Antibodies IMMUNOLOGY-

CiteScore

7.10

自引率

6.40%

发文量

审稿时长

11 weeks

期刊介绍： Antibodies (ISSN 2073-4468), an international, peer-reviewed open access journal which provides an advanced forum for studies related to antibodies and antigens. It publishes reviews, research articles, communications and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided. Electronic files or software regarding the full details of the calculation and experimental procedure - if unable to be published in a normal way - can be deposited as supplementary material. This journal covers all topics related to antibodies and antigens, topics of interest include (but are not limited to): antibody-producing cells (including B cells), antibody structure and function, antibody-antigen interactions, Fc receptors, antibody manufacturing antibody engineering, antibody therapy, immunoassays, antibody diagnosis, tissue antigens, exogenous antigens, endogenous antigens, autoantigens, monoclonal antibodies, natural antibodies, humoral immune responses, immunoregulatory molecules.