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

Molecular Therapy Oncology, vol. 32, pp. 200835

Abstract

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-1 low 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.

Authors 13

1. J. Fréderique de Graaf Aachen Immunetune BV

   Eurotransplant

   Affiliation as printed

   Immunetune BV, 2333 CH Leiden, the Netherlands

2. T. Pesic Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands

3. Felicia S. Spitzer Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands

4. Koen Oosterhuis Aachen Immunetune BV

   Eurotransplant

   Affiliation as printed

   Immunetune BV, 2333 CH Leiden, the Netherlands

5. Marcel G M Camps Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands

6. Iris Zoutendijk
   Affiliation as printed

   Synvolux BV, 2333 CH Leiden, the Netherlands

7. Bram Teunisse Aachen Immunetune BV

   Eurotransplant

   Affiliation as printed

   Immunetune BV, 2333 CH Leiden, the Netherlands

8. Wahwah Zhu
   Affiliation as printed

   Synvolux BV, 2333 CH Leiden, the Netherlands

9. Tsolère Arakelian Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands

10. Gerben C. M. Zondag Aachen Immunetune BV

    Eurotransplant

    Affiliation as printed

    Immunetune BV, 2333 CH Leiden, the Netherlands

    Synvolux BV, 2333 CH Leiden, the Netherlands

11. Ramon Arens Aachen Department of Immunology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands

12. Jeroen van Bergen Aachen Immunetune BV

    Eurotransplant

    Affiliation as printed

    Immunetune BV, 2333 CH Leiden, the Netherlands

13. FERRY A. OSSENDORP corresponding Aachen Department of Immunology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands