Researchers at the Indian Institute of Science (IISc) have designed a synthetic compound (antigen) that can latch onto a protein in the blood and hitchhike a ride to the lymph node, where it can boost the production of antibodies against cancer cells.
According to the researchers this approach gives a new direction to develop vaccine candidates for a variety of cancers.
“Inside the human body, cancer cells can weaken or shut down the production of antibodies that target and eliminate them. Developing a cancer vaccine, therefore, involves modifying or creating a mimic of an antigen found on the surface of cancer cells to turn up or turn on this antibody production. In recent years, scientists have turned to carbohydrates found on cancer cell surfaces to develop these antigens,” said ISc.
“Carbohydrate-based antigens have enormous importance and relevance in cancer vaccine development. One major reason is that both normal and abnormal (cancer) cells have large amounts of carbohydrates coating their surfaces. But the abnormal cells carry carbohydrates that are very heavily truncated,” said N. Jayaraman, Professor at the Department of Organic Chemistry.
Scientists have previously tried ferrying such antigens into the body using an artificial protein or virus particle as the carrier. But these carriers can be bulky, lead to side effects, and sometimes reduce antibody production against cancer cells. The IISc team, instead, decided to exploit the carrying ability of a natural protein called serum albumin, the most abundant protein in blood plasma.
To design the compound, the researchers zeroed in on a truncated carbohydrate called Tn found on the surface of a variety of cancer cells and synthesized it in the lab. Then, they combined it with a long-chain, oil-loving chemical — unlike carbohydrates, which are water-loving — to form bubble-like micelles. They found that the combination binds strongly to human serum albumin.
The researchers injected the compound into mice models to track its uptake and effect on the immune response. They found that the antigen accumulated largely in lymph nodes, the sites of key cellular mechanisms involved in the body’s immune response, including the activation of killer T cells and antibody production.
IISc said that the team is hopeful that the compound can be taken forward for vaccine development and clinical trials. “The Tn antigen is present on almost all cancer cells, including breast cancer and prostate cancer cells. By changing the type of antigen, we can target multiple cancers, “said PhD student Keerthana T.V.
