{"title":"Targeted cytokine delivery for cancer therapy through engineered mesenchymal stem cells","authors":"Pedram Yeganeh , Samin Forghani , Leili Pouresmaeil , Forough Parhizkar , Davood Jafari","doi":"10.1016/j.genrep.2025.102199","DOIUrl":null,"url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) have been identified as highly promising entities for the advancement of novel oncological therapies, attributable to their immunomodulatory functions, propensity to migrate towards neoplastic sites, and their ability to circumvent immune surveillance. This review meticulously discusses the potential of genetically modified MSCs to deliver cytokines, which serve as critical modulators of immune responses, for the purpose of targeted oncology treatment. MSCs can be modified through genetic engineering to produce various cytokines, such as interleukins (IL-21, IL-18, IL-12, IL-2) and interferons (IFN-γ, IFN-β, IFN-α). Upon the migration of these genetically modified MSCs to neoplastic sites, they are capable of releasing cytokines in the local microenvironment, thus enhancing anti-tumor immune responses and inducing apoptosis in malignant cells. Numerous preclinical investigations have demonstrated that MSCs engineered for cytokine production can markedly impede tumor progression and elevate survival rates across various oncological entities. Despite these promising results, significant challenges remain in bringing this approach to clinical practice. Key areas of ongoing research include refining delivery methods to ensure precise targeting of tumor sites and understanding the complex interplay between MSCs, cytokines, and the tumor microenvironment. This review underscores the potential of engineered MSCs as a promising strategy to address the limitations of conventional cytokine therapy. MSC-based therapies offer a targeted and efficient approach to cancer treatment, with the promise of improving patient outcomes and enhancing the overall efficacy of cancer treatment.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102199"},"PeriodicalIF":1.0000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S245201442500072X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Mesenchymal stem cells (MSCs) have been identified as highly promising entities for the advancement of novel oncological therapies, attributable to their immunomodulatory functions, propensity to migrate towards neoplastic sites, and their ability to circumvent immune surveillance. This review meticulously discusses the potential of genetically modified MSCs to deliver cytokines, which serve as critical modulators of immune responses, for the purpose of targeted oncology treatment. MSCs can be modified through genetic engineering to produce various cytokines, such as interleukins (IL-21, IL-18, IL-12, IL-2) and interferons (IFN-γ, IFN-β, IFN-α). Upon the migration of these genetically modified MSCs to neoplastic sites, they are capable of releasing cytokines in the local microenvironment, thus enhancing anti-tumor immune responses and inducing apoptosis in malignant cells. Numerous preclinical investigations have demonstrated that MSCs engineered for cytokine production can markedly impede tumor progression and elevate survival rates across various oncological entities. Despite these promising results, significant challenges remain in bringing this approach to clinical practice. Key areas of ongoing research include refining delivery methods to ensure precise targeting of tumor sites and understanding the complex interplay between MSCs, cytokines, and the tumor microenvironment. This review underscores the potential of engineered MSCs as a promising strategy to address the limitations of conventional cytokine therapy. MSC-based therapies offer a targeted and efficient approach to cancer treatment, with the promise of improving patient outcomes and enhancing the overall efficacy of cancer treatment.
Gene ReportsBiochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍:
Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.