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Published on: February 24, 2023
DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
Nadia Viborg1,2, Michail Angelos Pavlidis1, Marina Barrio-Calvo1
1Evaxion Biotech, Hørsholm, Denmark.
Abstract:
Recent findings have positioned tumor mutation-derived neoepitopes as attractive targets for cancer immunotherapy. Cancer vaccines that deliver neoepitopes via various vaccine formulations have demonstrated promising preliminary results in patients and animal models. In the presented work, we assessed the ability of plasmid DNA to confer neoepitope immunogenicity and anti-tumor effect in two murine syngeneic cancer models. We demonstrated that neoepitope DNA vaccination led to anti-tumor immunity in the CT26 and B16F10 tumor models, with the long-lasting presence of neoepitope-specific T-cell responses in blood, spleen, and tumors after immunization. We further observed that engagement of both the CD4+ and CD8+ T cell compartments was essential to hamper tumor growth. Additionally, combination therapy with immune checkpoint inhibition provided an additive effect, superior to either monotherapy. DNA vaccination offers a versatile platform that allows the encoding of multiple neoepitopes in a single formulation and is thus a feasible strategy for personalized immunotherapy via neoepitope vaccination.
Insights
Neoepitope DNA vaccination effectively generates anti-tumor immunity and lasting T-cell responses in mouse models. Combining DNA vaccines with immune checkpoint inhibitors enhances anti-tumor effects for personalized cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Tumor mutation-derived neoepitopes are promising targets for cancer immunotherapy.
- Neoepitope delivery via cancer vaccines shows potential in preclinical and clinical studies.
Purpose of the Study:
- To evaluate plasmid DNA's efficacy in inducing neoepitope immunogenicity and anti-tumor effects.
- To assess neoepitope DNA vaccination in syngeneic mouse cancer models.
Main Methods:
- Administered neoepitope DNA vaccination in CT26 and B16F10 murine cancer models.
- Monitored neoepitope-specific T-cell responses in blood, spleen, and tumors.
- Investigated the role of CD4+ and CD8+ T cells in tumor growth inhibition.
- Evaluated combination therapy with immune checkpoint inhibitors.
Main Results:
- Neoepitope DNA vaccination induced significant anti-tumor immunity in both models.
- Long-lasting neoepitope-specific T-cell responses were observed post-vaccination.
- Both CD4+ and CD8+ T cell responses were crucial for impeding tumor growth.
- Combination therapy demonstrated additive anti-tumor effects, outperforming monotherapy.
Conclusions:
- Neoepitope DNA vaccination is a viable strategy for inducing anti-tumor immunity.
- The combination of DNA vaccination and immune checkpoint inhibition offers a superior therapeutic approach.
- DNA vaccination platforms are adaptable for personalized neoepitope-based cancer immunotherapy.
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