# The Immunogenicity and Anti-tumor Efficacy of a Rationally Designed Neoantigen Vaccine for B16F10 Mouse Melanoma

Article · Zhang Y, Lin Z, Wan Y, Cai H, Deng L, Li R

- Archive id: doi:10.3389/fimmu.2019.02472
- Published: 2019-11-05
- Venue: Frontiers in immunology
- DOI: https://doi.org/10.3389/fimmu.2019.02472
- PMID: 31749795
- PMCID: PMC6848027
- Citations: 18
- Source URL: https://doi.org/10.3389/fimmu.2019.02472
- PDF: https://europepmc.org/articles/PMC6848027/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines)

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