Vaccination with GD3 synthase provides tumor protection against melanoma in mice (P4461)

Abstract

Abstract Expression of GD3 synthase (GD3s) in cells defines upregulated GD3 expression by melanoma tumor cells. GD3 presented in the context of CD1d is recognized by invariant NKT cells, which can generate cytokines conducive to anti-tumor responses. We hypothesized that DNA vaccination with GD3s could induce effective anti-tumor responses targeting GD3. C57BL/6 mice were subjected to weekly gene gun vaccination introducing DNA encoding either GD3s and adjuvant HSP70i, or TRP-1 ee/ng and HSP70i, versus empty vector DNA as control groups. Mice were challenged with 2.5x105 B16 mouse melanoma cells. Tumor growth was followed and any remaining tumor was resected for fluorocytometric analysis of immune infiltrates and cytokine expression by qRT-PCR. hGD3s-based vaccination provided similar protection from a B16 tumor challenge as the positive control group (60 and 62% reduced tumor sizes at 19 days, respectively). hGD3s vaccinated mice showed increased NKT abundance (2.27% ) compared to TRP-1 (1.11%) or empty vector (0.74%) among vaccinated mice. Increased CD8+ (3.3-fold), and CD4+ (1.2-fold) compared to the negative control group were also observed, combined with an increased abundance in IL-4 and IL-17 transcripts. In conclusion, GD3s based vaccination provided anti-tumor protection associated with inflammatory cytokine expression and increased (NK)T cell recruitment to tumor sites, offering an attractive concept for melanoma treatment.