{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329498/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Other","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329498"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Antigen-scaffolds loaded with hyper-stable Neoleukin-2/15 expand antigen-specific T cells with a favorable phenotype for adoptive cell therapy","description":"Adoptive cell therapy (ACT) has shown promising results in cancer treatment, however, achieving effective ex vivo expansion of potent, functionally active, and cytotoxic T cells remains challenging. To address this challenge, we recently developed artificial antigen-presenting scaffolds (Ag-scaffolds) capable of expanding antigen-specific T cells with phenotypes favorable for ACT. In this study, we compared the established technology using IL2/IL21-loaded Ag-scaffolds (Ag-IL2/21) with Neoleukin-2/15-loaded Ag-scaffolds (Ag-Neo2/15). Neoleukin-2/15 (Neo2/15) is an engineered cytokine that selectively binds to IL-2Rβ/γ receptors, enhancing CD8+ T cell proliferation while limiting regulatory T cell expansion. Based on its favorable signaling properties, we hypothesized that incorporating Neo2/15 as part of the Ag-scaffolds would improve the quality and functionality of expanded T cells. We showed that Ag-Neo2/15 scaffolds promoted significant T-cell expansion, with frequencies of antigen-specific CD8+ T cells comparable to those achieved with Ag-IL2/21 scaffolds. The CD8+ T cells expanded with Ag-Neo2/15 scaffolds exhibited potent TNFα and IFNγ, potentially enhancing their therapeutic potential. T cells expanded with Ag-Neo2/15 scaffolds had superior and durable cytotoxicity against tumor target cells compared to T cells expanded with Ag-IL2/21 scaffolds. These findings were further supported by our single-cell analysis revealing that T cells expanded with Ag-Neo2/15 scaffolds had higher cytotoxic scores and lower dysfunctionality scores compared to T cells expanded with Ag-IL2/21 scaffolds. The single-cell analysis also indicated increased expression of genes linked to cell division and enhanced proliferative capacity in Ag-Neo2/15 expanded T cells. Furthermore, TCR clonality analysis demonstrated that Ag-Neo2/15 scaffolds promoted the expansion of functionally superior T-cell clones, as the top clones of CD8+ T cells expanded with Ag-Neo2/15 scaffolds exhibited a favorable phenotype, essential for effective antigen recognition and sustained T-cell mediated cytotoxicity. Our findings suggest that Ag-Neo2/15 scaffolds represent an advancement in ACT by producing high-quality, functional antigen-specific T cells. This method has the potential to improve clinical outcomes in cancer therapy by generating large numbers of highly functional T cells, thereby optimizing the balance between cytotoxicity and proliferation capacity with less exhausted T-cells in expansion protocols.","dates":{"publication":"2026/05/01"},"accession":"GSE329498","cross_references":{"GSM":["GSM9705102","GSM9705101","GSM9705100"],"GPL":["34281"],"GSE":["329498"],"taxon":["Homo sapiens"]}}