Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
For full article and contact information, see Angew. Chem. Int. Ed. 1999, 38 (4), 563 - 566
On the right track
A synthetic carbohydrate sends
antibodies on the hunt for cancer cells
Many tumor cell surfaces contain proteins that in turn contain specific carbohydrates. These glycoproteins are often characteristic of cancer cells - a kind of "distinguishing mark" that could be included on a "wanted" poster. If the human immune system could be set on the trail of these glycoproteins, it could selectively recognize and destroy the cancer cells. Samuel J. Danishefsky, Philip O. Livingston, and their co-workers at the Sloan-Kettering Institute for Cancer Research in New York have reproduced the carbohydrate component of such a glycoprotein - and have indeed been able to use it to send human antibodies on the hunt for prostate and breast cancer cells.
The long-term goal of these workers is a kind of "vaccine" against cancer, with which wandering cancer cells could be trapped before developing into the "dreaded" metastases. "The first clinical trials with our Globo-H-antigen are encouraging," says Danishefsky. The carbohydrate molecule that he and his team copied from nature was initially discovered on the coating of breast cancer cells, and was later also detected in prostate cancer and some normal tissue cells; it consists of six characteristically linked sugar molecules. Once the team working with Danishefsky and Livingston had synthesized this complex molecule, they tested it carefully on mice. Later, they used it to inoculate twenty cancer patients.
The results of this study really make one sit up and take notice: The sera obtained from the blood of patients after the inoculation, did indeed react with the glycoproteins, which the researchers previously had isolated from tumor cells. This clearly demonstrates that the synthetic carbohydrate shifts the immune system into a state that also recognizes the natural, tumor-specific glycoproteins. The antibodies that the patients formed against the synthetic tumor molecule then also reacted with the cancer’s glycoproteins, when they encountered them in their "natural environment", that is, on the surface of cells.
These experiments show that the principle of a vaccine against cancer cells can work; whether it can be used in treatment in a few years must be determined by further clinical trials.