G(M2)-KLH CONJUGATE VACCINE - INCREASED IMMUNOGENICITY IN MELANOMA PATIENTS AFTER ADMINISTRATION WITH IMMUNOLOGICAL ADJUVANT QS-21

The cell surface gangliosides G(M2), G(D2), and G(M3), are often overe xpressed in malignant melanoma. We have shown previously that immuniza tion of melanoma patients with G(M2) and Bacillus Calmette-Guerin indu ced an IgM antibody response in most patients and that patients with h igh titer G(M2) antibodies showed increased survival. As is commonly s een with carbohydrate antigens (which are T independent), the IgM resp onse was short lived, and an IgG response was rarely observed. To incr ease immunogenicity, we conjugated G(M2) covalently with keyhole limpe t hemocyanin (KLH). G(M2)-KLH vaccine was given to melanoma patients a lone or with one of the three adjuvants: Bacillus Calmette-Guerin, DET OX, 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 respo nse, and a consistent IgG response (isotype IgG1 and IgG3). It also in duced the highest titer anti-KI,II 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, s uch as G(D2) and G(D3), and to determine the effects of ganglioside an tibodies on the course of melanoma. In addition, the finding that QS-2 1 significantly increased the immunogenicity of G(M2)-KLH suggests tha t it may do the same for other conjugate vaccines, many of which are c urrently used without adjuvant.