Despite melanoma immunogenicity and remarkable therapeutic effects of negative immune checkpoint inhibitors, a significant fraction of patients does not respond to current treatments. This could be due to limitations in tumor immunogenicity and profound immunosuppression in the melanoma microenvironment. Moreover, insufficient tumor antigen processing and presentation by dendritic cells (DC) may hamper the development of tumor-specific T cells. Using two genetically engineered mouse melanoma models (RET and BRAFV600E transgenic mice), in which checkpoint inhibitor therapy alone is not efficacious, we performed proof-of-concept studies with an improved, multivalent DC vaccination strategy based on our recently developed genetic mRNA cancer vaccines. The in vivo expression of multiple chimeric MHC class I receptors allows a simultaneous presentation of several melanoma-associated shared antigens tyrosinase related protein (TRP)-1, tyrosinase, human glycoprotein 100 and TRP-2. The DC vaccine induced a significantly improved survival in both transgenic mouse models. Vaccinated melanoma-bearing mice displayed an increased CD8 T cell reactivity indicated by a higher IFN-γ production and an upregulation of activation marker expression along with an attenuated immunosuppressive pattern of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). The combination of DC vaccination with ultra-low doses of paclitaxel or anti-PD-1 antibodies resulted in further prolongation of mouse survival associated with a stronger reduction of MDSC and Treg immunosuppressive phenotype. Our data suggest that an improved multivalent DC vaccine based on shared tumor antigens induces potent anti-tumor effects and could be combined with checkpoint inhibitors or targeting immunosuppressive cells to further improve their therapeutic efficiency.
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 August 2022.
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#39
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Altmetric has tracked 27,788,586 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 2,232 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one has gotten more attention than average, scoring higher than 68% of its peers.
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