New method of cancer immunotherapy developed
A team of scientists has discovered a novel form of cancer immunotherapy, which works by removing certain sugars from the surface of cancer cells and making those cells visible to the immune system. Scientists have long known that if certain sugars are present on a tumor, it is less likely to respond well to therapies.
But nobody knew what that halo of sugars was doing, in part because such a small number of labs study the glycocalyx.
Evidence had been mounting within those few labs that do study the glycocalyx, including Bertozzi’s, that a subset of sugars called sialic acids act as a signal for the innate immune system to ignore the otherwise suspicious-looking tumor. Eliminate those sugars, and maybe innate immune cells would be more likely to recognize and attack the cancer cells, Bertozzi thought.
And essentially that’s exactly what happened. Current immunotherapies on the market work by blocking one of the inhibitory signals that are recognized by the adaptive immune system. Block those and the balance tilts in such a way that the immune system will attack the now recognizable cancer.
Bertozzi’s approach provides a second way of tiling the balance in favor of attack, this time for the innate immune system. She said this study shows just one example of how it could work, but her sugar-removing lawnmower could be used on a wide variety of cell types, not just those expressing HER2, and on different types of sugars.
Successful tumors are able to evade the immune system, which is otherwise capable of killing transformed cells. Therapies that prevent this evasion have become revolutionary treatments for incurable cancers. One mechanism of evasion is the presentation of sugars, called sialic acids, within the cell surface’s sugar coating, or glycocalyx.
Here, we designed biotherapeutic molecules, termed “antibody–enzyme conjugates,” that selectively remove sialic acids from tumor cells. The antibody directs the enzyme to the cancer cells, the enzyme cleaves the sugars, and then the antibody directs immune cells to kill the desialylated cancer cells. The conjugate increased tumor cell killing compared with the antibody alone. Editing the cancer cell glycocalyx with an antibody–enzyme conjugate represents a promising approach to cancer immune therapy.