GSE262852 Neoantigen-Augmented iPSC-based Cancer Vaccine Combined with Local Radiotherapy Promotes Systemic Antitumor Immunity in Poorly Immunogenic Cancers

Contributors : Kevin C Huang ; William T Chen ; Jia-Yi Chen ; Chien-Yueh Lee ; Chia-Hsin Wu ; Chia-Ying Lai ; Pei-Chen Yang ; Ji-An Liang ; An ‑Cheng Shiau ; K S Chao ; Tao-Wei KeSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAlthough irradiated induced-pluripotent stem cells (iPSCs) as a prophylactic cancer vaccine elicit an antitumor immune response, the therapeutic efficacy of iPSC-based cancer vaccines is not promising due to their insufficient antigenicity and the immunosuppressive tumor microenvironment. Here, we found that neoantigen-engineered iPSC cancer vaccines can trigger neoantigen-specific T cell responses to eradicate cancer cells and increase the therapeutic efficacy of RT in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC). We generated neoantigen-augmented iPSCs (NA-iPSCs) by engineering AAV2 vector carrying murine neoantigens and evaluated their therapeutic efficacy in combination with radiotherapy. After administration of NA-iPSC cancer vaccine and radiotherapy, we found that ~60% of tumor-bearing mice achieved a complete response in microsatellite-stable CRC model. Furthermore, splenocytes from mice treated with NA-iPSC plus RT produced high levels of IFN  secretion in response to neoantigens and had a greater cytotoxicity to cancer cells, suggesting that the NA-iPSC vaccine combined with radiotherapy elicited a superior neoantigen-specific T-cell response to eradicate...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research