VERY-LOW-DENSITY LIPOPROTEINS AND INTERLEUKIN-2 ENHANCE THE IMMUNOGENICITY OF 9-O-ACETYL-GD3 GANGLIOSIDE IN BALB C MICE/

Gangliosides expressed by tumor cells constitute potential targets for immunotherapy. A major limitation of protocols aiming to immunize pat ients against tumor gangliosides is the weak immunogenicity of these m olecules. We have previously shown that exogenous gangliosides are ess entially bound to serum lipoproteins. Ln this study we have analyzed t he influence of human serum lipoproteins on the immunogenicity of puri fied human ganglioside 9-O-acetyl-GD3 in BALB/c mice. Although express ed at very low levels in mice, this ganglioside was not immunogenic wh en administered in the form of micelles. However 9-O-acetyl-GD3 adsorb ed onto Very Low Density Lipoproteins (VLDL) was strongly and reproduc ibly immunogenic, inducing both an IgM and an IgG response, with highe r titers than those obtained with total serum. The IgM antibody respon se appeared after a single injection whereas the IgG response was obse rved after 3 weeks but was stronger and more durable. The antibody res ponse to 9-O-acetyl-GD3 bound to other serum fractions was weak or abs ent. The addition of recombinant interleukin 2 (IL-2) enhanced weak an tibody responses to 9-O-acetyl-GD3 thereby facilitating responses to g anglioside in micelles and in protein-free Very Low Density Particles. Using in vitro assays, we demonstrated that VLDL-bound ganglioside C- 14-GM3 was more sensitive to the effect of neuraminidase than ganglios ides bound to other lipoprotein fractions, suggesting greater accessib ility of VLDL-bound gangliosides. These results indicate that VLDL-bou nd gangliosides are the most immunologically active fraction of serum gangliosides. VLDL or similar particles and recombinant IL-2 may be us eful adjuvants for immunization with gangliosides. (C) 1997 Elsevier S cience B.V.