GM2-KLH Conjugate Vaccine: Increased Immunogenicity in Melanoma Patients after Administration with Immunological Adjuvant QS-21

Abstract The cell surface gangliosides G M2 , G D2 , and G D3 are often overexpressed in malignant melanoma. We have shown previously that immunization of melanoma patients with G M2 and Bacillus Calmette-Guerin induced an IgM antibody response in most patients and that patients with high titer G M2 antibodies showed increased survival. As is commonly seen with carbohydrate antigens (which are T independent), the IgM response was short lived, and an IgG response was rarely observed. To increase immunogenicity, we conjugated G M2 covalently with keyhole limpet hemocyanin (KLH). G M2 -KLH vaccine was given to melanoma patients alone or with one of the three adjuvants: Bacillus Calmette-Guerin , DE-TOX, or QS-21. The most effective vaccine was G M2 -KLH with QS-21. It induced a much higher titer, a longer-lasting IgM G M2 antibody response, and a consistent IgG response (isotype IgG1 and IgG3). It also induced the highest titer anti-KLH response. The results suggest that the conjugate G M2 -KLH plus QS-21 vaccine elicited significant T-cell help. Because there was no serious toxicity, this vaccine approach is attractive for augmenting the immunogenicity of other gangliosides, such as G D2 and G D3 , and to determine the effects of ganglioside antibodies on the course of melanoma. In addition, the finding that QS-21 significantly increased the immunogenicity of G M2 -KLH suggests that it may do the same for other conjugate vaccines, many of which are currently used without adjuvant.