Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer

Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer

CD4+ T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC...

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Main Authors: Joanna Fréderique de Graaf, Tamara Pesic, Felicia S. Spitzer, Koen Oosterhuis, Marcel G.M. Camps, Iris Zoutendijk, Bram Teunisse, Wahwah Zhu, Tsolere Arakelian, Gerben C. Zondag, Ramon Arens, Jeroen van Bergen, Ferry Ossendorp
Format: Article
Language:English
Published: Elsevier 2024-09-01
Series:Molecular Therapy: Oncology
Subjects:
MT: Regular Issue
DNA vaccine
cancer vaccine
neoantigens
personalized medicine
immunotherapy
Online Access:http://www.sciencedirect.com/science/article/pii/S2950329924000778
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Summary:CD4+ T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC-38 colon carcinoma, encoding CD8+ T cell neoantigens alone (noHELP) or in combination with either “universal” helper antigens (uniHELP) or helper neoantigens (neoHELP). Both types of helped vaccines increased the frequency of vaccine-induced CD8+ T cells, and particularly uniHELP increased the fraction of KLRG1+ and PD-1low effector cells. However, when mice were subsequently injected with MC-38 cells, only neoHELP vaccination resulted in significantly better tumor control than noHELP. In contrast to uniHELP, neoHELP-induced tumor control was dependent on the presence of CD4+ T cells, while both vaccines relied on CD8+ T cells. In line with this, neoHELP variants containing wild-type counterparts of the CD4+ or CD8+ T cell neoantigens displayed reduced tumor control. These data indicate that optimal personalized cancer vaccines should include MHC class II-restricted neoantigens to elicit tumor-specific CD4+ T cell help.
ISSN:2950-3299

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