Using the MHC-II-negative murine colon carcinoma model MC38, Graaf and Pesic et al. compared tumor-specific and tumor-unrelated CD4+ T cell helper antigens in neoantigen vaccination. Compared to no-HELP (CD8+ T cell neoantigens alone), neoHELP (with tumor-specific helper neoantigens) and uniHELP (with universal helper antigens) improved vaccine-induced CD8+ T cell response. Although uniHELP showed pronounced circulating CD8+ T responses, only neoHELP vaccination protected against the MC38 tumors in a CD4+ and CD8+ T cell-dependent manner and induced changes in CD8+ T cells that were consistent with a more effector phenotype.
Contributed by Shishir Pant
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.
Author Info: (1) Immunetune BV, 2333 CH Leiden, the Netherlands. (2) Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. (3) Department of Immunology, L
Author Info: (1) Immunetune BV, 2333 CH Leiden, the Netherlands. (2) Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. (3) Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. (4) Immunetune BV, 2333 CH Leiden, the Netherlands. (5) Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. (6) Synvolux BV, 2333 CH Leiden, the Netherlands. (7) Immunetune BV, 2333 CH Leiden, the Netherlands. (8) Synvolux BV, 2333 CH Leiden, the Netherlands. (9) Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. (10) Immunetune BV, 2333 CH Leiden, the Netherlands. Synvolux BV, 2333 CH Leiden, the Netherlands. (11) Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. (12) Immunetune BV, 2333 CH Leiden, the Netherlands. (13) Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
