Logo do repositório
 
Publicação

Mannan-targeting chimeric antigen receptor redirected antifungal activity of NK-92 cells against Candida albicans

2025-08Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorde Campos, Gabriela Yamazaki
dc.contributor.authorGuimarães, Júlia Garcia
dc.contributor.authorMachado, Michele Procópio
dc.contributor.authorOliveira-Brito, Patrícia Kellen Martins
dc.contributor.authorShin, Ben
dc.contributor.authorMaio, Antonio Di
dc.contributor.authordos-Santos, Douglas
dc.contributor.authorPalma, Patricia Vianna Bonini
dc.contributor.authordos Reis, Thaila Fernanda
dc.contributor.authorGoldman, Gustavo Henrique
dc.contributor.authorPalma, Angelina S.
dc.contributor.authorMatthews, Steve J.
dc.contributor.authorFeizi, Ten
dc.contributor.authorLiu, Yan
dc.contributor.authorda Silva, Thiago Aparecido
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.institutionFaculdade de Ciências e Tecnologia (FCT)
dc.contributor.pblElsevier
dc.date.accessioned2025-08-19T21:20:39Z
dc.date.available2025-08-19T21:20:39Z
dc.date.issued2025-08
dc.descriptionFunding Information: This work was supported by the Funda\u00E7\u00E3o de Amparo \u00E0 Pesquisa do Estado de S\u00E3o Paulo (Grant numbers 2023/06496-0 ; 2022/14669-9 ; 2021/02758-4 ; 2020/16738-2 ; 2019/26074-7 ; 2018/18538-0 ) to TAS and GYC, and National Institute of Science and Technology in Human Pathogenic Fungi (Conselho Nacional de Desenvolvimento Cient\u00EDfico e Tecnol\u00F3gico, CNPq; grant number 405934/2022-0 ) to GHG and TAS. Funding Information: GYC and TAS conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. JGG, MPM, PKMOB, BS, ADM, YL, SJM, and TF performed the experiments, analyzed the data, prepared figures and/or tables, and approved the final draft. DS, PVBP, TFR, and GHG performed the experiments and approved the final draft. ASP (performed the experiments and approved the final draft). All animal experiments were approved by the Committee on Ethics in Animal Research of Ribeir\u00E3o Preto Medical School (protocol 071/2021). C. auris (clinical isolates 467, 468, and 469) were available to make a library of GHG.\u2019s lab, and the Committee of Ethics of the University of S\u00E3o Paulo, Campus of Ribeir\u00E3o Preto, Brazil (Permit Number 08.1.1277.53.6; studies on the interaction of fungal pathogens with animals) approved all protocols to work with clinical isolates. This work was supported by the Funda\u00E7\u00E3o de Amparo \u00E0 Pesquisa do Estado de S\u00E3o Paulo (Grant numbers 2023/06496-0; 2022/14669-9; 2021/02758-4; 2020/16738-2; 2019/26074-7; 2018/18538-0) to TAS and GYC, and National Institute of Science and Technology in Human Pathogenic Fungi (Conselho Nacional de Desenvolvimento Cient\u00EDfico e Tecnol\u00F3gico, CNPq; grant number 405934/2022-0) to GHG and TAS. The glycan microarray studies were performed in the Carbohydrate Microarray Facility at the Glycosciences Laboratory with support from Wellcome Trust Biomedical Resource grants (099197/Z/12/Z, 108430/Z/15/Z, and 218304/Z/19/Z) and in part by the March of Dimes Prematurity research center grant (22-FY18-82). The glycan microarrays contain many saccharides provided by collaborators whom we thank, as well as members of the Glycosciences Laboratory for their contribution in the establishment of the NGL-based microarray system. The funders had no role in study design, data collection and analysis, publication decisions, or manuscript preparation [ 62\u201364]. Funding Information: The glycan microarray studies were performed in the Carbohydrate Microarray Facility at the Glycosciences Laboratory with support from Wellcome Trust Biomedical Resource grants (099197/Z/12/Z, 108430/Z/15/Z, and 218304/Z/19/Z) and in part by the March of Dimes Prematurity research center grant (22-FY18-82). The glycan microarrays contain many saccharides provided by collaborators whom we thank, as well as members of the Glycosciences Laboratory for their contribution in the establishment of the NGL-based microarray system. Publisher Copyright: © 2025 International Society for Cell & Gene Therapy
dc.description.abstractChimeric antigen receptors (CARs) offer promising prospects for innovative cell-based therapies against invasive fungal infections such as invasive candidiasis. Here, we have developed 4 CARs targeting Candida albicans with distinct single-chain variable fragments (scFvs): scFv3-CAR, scFv5-CAR, scFv12-CAR, and scFvκ3-1-CAR. In T cells, scFv5-CAR induced IL-2 expression in response to C. albicans hyphae, while scFv3-CAR and scFv12-CAR did not mediate cell activation against C. albicans. Notably, scFvκ3-1-CAR mediated the strongest cell activation against C. albicans yeast, hyphae, and other clinically relevant Candida species. scFvκ3-1-CAR-NK-92 cells exhibited elevated IFN-γ and CD107a expression, reducing C. albicans viability. NOD scid gamma (NSG) mice treated with scFvκ3-1-CAR-NK-92 cells had reduced C. albicans burden in the kidneys 24 hours postinfection. We showed that scFvκ3-1-CAR targets C. albicans mannan but no other glycans in glycan microarray screening analyses. These findings reveal the scFvκ3-1-CAR potential as a therapeutic strategy for treating Candida spp. by modifying peripheral blood mononuclear cells.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent16
dc.format.extent4249182
dc.identifier.doi10.1016/j.jcyt.2025.05.001
dc.identifier.issn1465-3249
dc.identifier.otherPURE: 126497019
dc.identifier.otherPURE UUID: db5c793b-2c84-494b-bd3f-dabab1a034c1
dc.identifier.otherScopus: 105008105718
dc.identifier.otherPubMed: 40498437
dc.identifier.otherORCID: /0000-0001-5797-6555/work/190142099
dc.identifier.urihttp://hdl.handle.net/10362/186641
dc.identifier.urlhttps://www.scopus.com/pages/publications/105008105718
dc.language.isoeng
dc.peerreviewedyes
dc.subjectCandida albicans
dc.subjectCAR-NK cells
dc.subjectCAR-T cells
dc.subjectchimeric antigen receptor
dc.subjectinvasive candidiasis
dc.subjectmannan
dc.subjectImmunology and Allergy
dc.subjectImmunology
dc.subjectOncology
dc.subjectGenetics(clinical)
dc.subjectCell Biology
dc.subjectTransplantation
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleMannan-targeting chimeric antigen receptor redirected antifungal activity of NK-92 cells against Candida albicansen
dc.typejournal article
degois.publication.firstPage917
degois.publication.issue8
degois.publication.lastPage932
degois.publication.titleCytotherapy
degois.publication.volume27
dspace.entity.typePublication
rcaap.rightsopenAccess

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
1-s2.0-S1465324925007091-main.pdf
Tamanho:
4.05 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

Home collection (FCT)