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Polysaccharides Unique Targets for Immunotherapy

Polysaccharides Unique Targets for Immunotherapy

ORLANDO—Polysaccharides
(a type of carbohydrate) are the most highly expressed antigens on the surface
of cancer cells, and they can be uniquely effective targets for immunotherapy,
said Philip Livingston, MD, of Memorial Sloan-Kettering Cancer Center and
Cornell University Medical College.

He spoke at a symposium held in conjunction with the 38th
Annual Meeting of the American Society of Clinical Oncology (ASCO) and
supported by Anti-genics Inc. and the University of Connecticut School of
Medicine.

The immune response to polysaccharide antigens is largely
limited to the production of antibodies, Dr. Livingston said. In addition to
cellular immune mechanisms, antibodies have been shown to be important
mediators of autoimmunity, such as with graft rejections. "You can induce
autoimmunity against almost any organ in the body experimentally," he said,
"and some of this is antibody mediated."

Dr. Livingston explained that the efficacy of antibodies
against polysaccharide targets on cancer cells has been demonstrated in animal
models. In one study, mice were challenged with the EL4 lymphoma cell line,
which naturally expresses the carbohydrate ganglioside GD2. Mice that received
a monoclonal antibody directed against GD2 within 2 to 4 days after tumor
challenge were protected from tumor progression. However, mice that received
the antibody 7 to 10 days following tumor challenge showed little benefit.

He also pointed out that when lower numbers of tumor cells
were used as a challenge, the window of opportunity for effective protection
with the antibodies was longer. "The message is that for antibodies or vaccines
that induce antibodies to be effective, you need to be thinking micrometastases
and the adjuvant setting," he said.

There are several defined cancer cell surface antigens that
can induce tumor cell regression through antibody mechanisms. The majority of
these antigens, including the gangliosides GM2, GD2, and GD3, and fucosyl GM1,
are carbohydrates, Dr. Livingston said. The GM2, GD2, and GD3 gangliosides are
strongly expressed on the surface of more than 50% of tumors, including
melanomas, neuroblastomas, and sarcomas.

On their own, he said, the tumor-related carbohydrate
antigens are only weakly immunogenic. Immunogenicity is greatly increased by
chemically linking the carbohydrate to a carrier protein and mixing that with
an adjuvant.

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