IsoPlexis’ Functional Proteomics Identifies Protective immunity of Polyfunctional T Cells in Mice Inoculated with the Vaccine
We previously discussed the importance of developing vaccines that induce protective immunity and that nanoparticles have been shown to be an ideal delivery system. This study has now been published in Frontiers in Immunology. “Targeted Co-delivery of Tumor Antigen and α-Galactosylceramide to CD141+ Dendritic Cells Induces a Potent Tumor Antigen-Specific Human CD8+ T Cell Response in Human Immune System Mice” by Huang et al. discusses a nanovaccine designed to promote anti-tumor response in humanized mice and how IsoPlexis’ single-cell proteomics was able to predict the outcome of this novel vaccine.
While previous studies have demonstrated that co-delivering antigens Ag and α-galactosylceramide (α-GalCer) to dendritic cells (DCs) have harnessed the helper functions of invariant Natural Killer T (iNKT) cells, they did not test the function of iNKT cells in a human in vivo setting. Researchers Huang et al. designed a nanoparticle-based vaccine to target human CD141+ dendritic cells while co-delivering tumor antigens Melan A and α-GalCer (an NK cell agonist).1 This vaccine was tested using a humanized mouse model, which mimics the human immune system. Researchers used IsoPlexis’ single-cell proteomics to identify highly polyfunctional CD8+ T cells (the murine equivalent of CD141+ DCs), which were induced by the nanovaccine. This data reveals the predictive potential for vaccine potency. The upregulated polyfunctional response of these CD8+ T cell subsets correlate with Melan-A-specific T cells that are associated with anti-tumor immunity in vaccinated humanized mice.1 IsoPlexis’ highly multiplexed functional proteomics provides predictive biomarkers and a unique tool for more accurate evaluation of tumor vaccine efficacy in a pre-clinical setting.
“This finding demonstrates for the first time the unique ability of human iNKT cells to license cross-priming DCs in vivo and adds a new dimension to the current strategy of cancer vaccine development.”1
Humanized Mouse Model Coupled with IsoPlexis’ Single-Cell Proteomics Accelerates Vaccine Development and Testing
IsoPlexis’ 32-plex single-cell highly-multiplexed proteomics platform allowed for the sensitive detection of polyfunctional human CD8+ T cell subsets in the humanized mice, which were secreting cytokines associated with anti-tumor function, induced by the novel nanovaccine. Polyfunctional cells are recognized as an important biomarker of immune response to antigen stimulation and this data demonstrates the predictive potential of polyfunctional cells in determining vaccine potency. Researchers also noted a higher PSI, a measure which combines both percentage of polyfunctional cells and intensities of secreted proteins. Furthermore, the upregulated PSI was found to be strongly predominated by proteins associated with anti-tumor function, suggesting that the vaccine used has high anti-cancer potential.1 The humanized mouse model allowed researchers Huang et al. to replicate the response of human iNKT cells accurately and evaluate a new strategy for testing vaccines.1
The use of nanovaccines and humanized mouse models are two novel techniques with great potential for the future of the field. IsoPlexis’ functional proteomics platform works in tandem with these techniques to define the precise function of single cells, identifying predictive cell subsets to accelerate the development of durable and potent vaccines. Access the full Frontiers in Immunology publication here and click here to access our roundtable with leading cancer immunology researchers and learn more about how IsoPlexis’ platform can provide critical insights in harnessing the immune system to treat cancers and other difficult-to-treat diseases.
- Huang J, et al. Targeted co-delivery of tumor antigen α-galactosylceramide to CD141+ dendritic cells induces a potent tumor antigen-specific human CD8+ T cell response in human immune system mice. Frontiers in Immunology 11: 2043, 2020.