Very low density lipoproteins and interleukin 2 enhance the immunogenicity of 9- O-acetyl-GD3 ganglioside in BALB/c mice

Abstract

Gangliosides expressed by tumor cells constitute potential targets for immunotherapy. A major limitation of protocols aiming to immunize patients against tumor gangliosides is the weak immunogenicity of these molecules. We have previously shown that exogenous gangliosides are essentially bound to serum lipoproteins. In this study we have analyzed the influence of human serum lipoproteins on the immunogenicity of purified human ganglioside 9- O-acetyl-GD3 in BALB/c mice. Although expressed at very low levels in mice, this ganglioside was not immunogenic when administered in the form of micelles. However 9- O-acetyl-GD3 adsorbed onto Very Low Density Lipoproteins (VLDL) was strongly and reproducibly immunogenic, inducing both an IgM and an IgG response, with higher titers than those obtained with total serum. The IgM antibody response appeared after a single injection whereas the IgG response was observed after 3 weeks but was stronger and more durable. The antibody response to 9- O-acetyl-GD3 bound to other serum fractions was weak or absent. The addition of recombinant interleukin 2 (IL-2) enhanced weak antibody responses to 9- O-acetyl-GD3 thereby facilitating responses to ganglioside in micelles and in protein-free Very Low Density Particles. Using in vitro assays, we demonstrated that VLDL-bound ganglioside 14 C -GM3 was more sensitive to the effect of neuraminidase than gangliosides bound to other lipoprotein fractions, suggesting greater accessibility of VLDL-bound gangliosides. These results indicate that VLDL-bound gangliosides are the most immunologically active fraction of serum gangliosides. VLDL or similar particles and recombinant IL-2 may be useful adjuvants for immunization with gangliosides.