NEW YORK--A mollusk protein turned out to be the best carrier for a cancer vaccine being developed by Philip O. Livingston, MD, at Memorial Sloan-Kettering Cancer Center. This approach to augmenting the immunogenicity of the GM2 ganglioside tumor antigen is about to be tested in phase III randomized trials of melanoma patients who are free of detectable disease after surgery but are at high risk for recurrence.
The trials will also test Dr. Livingston's long-held belief that purified antigens, not whole tumor cells, offer the most efficient method of immunization.
The new cancer vaccine combines the mollusk-derived keyhole limpet hemocyanin (KLH) molecule, a highly immunogenic carrier protein; saponin fraction QS-21, a potent immunological adjuvant purified from tree bark; and the GM2 ganglioside, a glycolipid found on the cell surface of tumors of neuroectodermal origin, including melanoma, sarcoma, and neuroblastoma.
'A Sea of Cytokines'
Use of this vaccine will create a "sea of cytokines," Dr. Livingston said at an international symposium on cancer vaccines sponsored by the Cancer Research Institute. The KLH will be broken down by dendritic cells and macrophages into thousands of epitopes, recognized by thousands of T cells. The cytokines stimulated by the vaccine will change as the immune response progresses from initial recognition to maturation, releasing a "flood of cytokines appropriate for each particular phase of the immune response against the core antigen (GM2)," Dr. Livingston said.
The cancer vaccines Dr. Livingston has been working on are designed to take the tumor au-toantigens out of their normal cell environment and put them in the context of foreign antigens.
"Tumor antigens are poor antigens because they are autoantigens, slightly modified, and because they are surrounded by autoantigens much like the rest of our normal antigens," he said. "But the antigens of various infectious disease are surrounded by other highly foreign antigens--and it seems as though the immune system has been designed to take advantage of this difference."