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

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 ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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