mProX™ Human XCR1 Stable Cell Line

Oyama R, et al. "An Ionizable Lipid Material with a Vitamin E Scaffold as an mRNA Vaccine Platform ." ACS nano, 2023.
The development of RNA vaccines encapsulated in lipid nanoparticles (LNPs) with in vitro transcribed mRNA (IVT-mRNA) has emerged as a promising modality for vaccinations. These vaccines have the ability to induce CD8(+) T-cell-mediated cellular immunity, which is crucial in eradicating pathogen-infected or cancerous cells from the body. A new ionizable lipid with a vitamin E scaffold has been incorporated into LNPs, leading to enhanced cellular immunity. This was demonstrated through the successful induction of cytotoxic T cell responses against a model antigen (ovalbumin) and the regression of an E.G7-OVA tumor model. Furthermore, vaccination with these LNPs provided protection against lethal Toxoplasma gondii infection, emphasizing the potential of this approach for vaccine development. The vitamin E scaffold also played a critical role in activating type I interferon response, which was found to be necessary for the differentiation of effector CD8(+) T cells induced by the mRNA-LNPs. Our study also revealed that conventional dendritic cells (cDCs) were essential for generating CD8(+) T cell responses, while a specialized subset of cDCs (cDC1) was not required. Interestingly, the LNPs selectively transfected a different subset of cDCs (cDC2), which migrated from the skin to lymph nodes and interacted with CD8(+) T cells. This highlights the importance of innate immune signaling and antigen presentation by cDC2 for the establishment of effective immunogenic responses.
Pubmed: 37814788   DOI: 10.1021/acsnano.3c02251

Truex NL, et al. "Enhanced Vaccine Immunogenicity Enabled by Targeted Cytosolic Delivery of Tumor ." ACS central science, 2023.
In this study, a group of researchers engineered a new antigen peptide delivery system in order to improve the efficacy of molecular vaccines. This system utilizes the nontoxic anthrax protein, protective antigen (PA), and a single-chain variable fragment (scFv) that targets the XCR1 receptor on dendritic cells (DCs). By combining these components, the delivery system was able to specifically target XCR1-positive cross-presenting DCs and facilitate the translocation of immunogenic epitope sequences. The results showed improved priming of antigen-specific T cells in vivo and significant suppression of tumor growth (up to 58%) and increased survival in mice bearing aggressive B16-F10 melanomas compared to free antigen. These findings demonstrate the potential of targeting DCs for cytosolic antigen delivery to enhance the immunogenicity and antitumor efficacy of cancer vaccines.
Pubmed: 37780364   DOI: 10.1021/acscentsci.3c00625