{"id":"doi:10.3389/fimmu.2019.02472","kind":"article","title":"The Immunogenicity and Anti-tumor Efficacy of a Rationally Designed Neoantigen Vaccine for B16F10 Mouse Melanoma","authors":["Zhang Y","Lin Z","Wan Y","Cai H","Deng L","Li R"],"author_count":6,"year":2019,"published":"2019-11-05","venue":"Frontiers in immunology","cited_by":18,"doi":"10.3389/fimmu.2019.02472","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3389/fimmu.2019.02472","archive_url":"https://space-kitty.com/papers/doi:10.3389/fimmu.2019.02472","updated":null,"pmid":"31749795","pmcid":"PMC6848027","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6848027/pdf","abstract":"Tumor neoantigens are ideal targets for cancer immunotherapy as they are recognized by host immune system as foreigners and can elicit tumor-specific immune responses. However, existing strategies utilizing RNA or long peptides for the neoantigen vaccines render limited immune responses since only 20-30% of neoantigens predicted in silico to bind MHC I molecules are capable of eliciting immune responses with the majority of responding T cells are CD4 + . Therefore, it warrants further exploration to enhance neoantigen-specific CD8 + T cells responses. Since neoantigens are naturally weak antigens, we asked whether foreign T help epitopes could enhance their immunogenicity. In present study, we chose 4 weak B16F10 neoantigens as vaccine targets, and fused them to the transmembrane domain of diphtheria toxin, namely DTT-neoAg. Strikingly, the vaccine elicited anti-tumor CD8 + T cells responses and enhanced tumor infiltration of both T cells and NK cells. Impressively, DTT-neoAg vaccine significantly deterred tumor growth with the inhibition rate reached 88% in the preventive model and 100% in the therapeutic model at low dose of tumor challenge. Furthermore, after second challenge with higher dose of tumor cells, 33.3% of the immunized mice remained tumor-free for 6 months in the therapeutic model. Because DTT is a non-toxic domain of diphtheria toxin, it may be not of great concern in terms of safety as a Th epitope provider. Thus, the fusion strategy employed by this study may become a feasible and powerful approach for development of personalized cancer vaccines.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"The Immunogenicity and Anti-tumor Efficacy of a Rationally Designed Neoantigen Vaccine for B16F10 Mouse Melanoma\" by Zhang Y, Lin Z, Wan Y et al., https://doi.org/10.3389/fimmu.2019.02472, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}