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
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."