Precision glycocalyx editing as a strategy for cancer immunotherapy

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.