Cellular reception: finding a cure for cancer through genetic immunology

Despite modern medicine and continuous research, diseases like HIV/AIDS and cancer are still taking victims. But significant progress has been made right here in Canada to one day find a method of stopping the diseases from growing in our bodies to begin with. An invaluable contributor to this goal is Tak Wah Mak, a Chinese-Canadian scientist who discovered the T-cell receptor, pioneered the study of genetics in relation to immunology and continues to make great strides in biochemistry to this very day.

T-cells are cells that look for antigens, which are invaders in the body, like pollen or a cold virus. Each T-cell is unique in that they’re programmed to find one specific antigen. Antigens get stuck to macrophages, which are white blood cells that round up these intruders for T-cells. Mak first identified the receptors on a T-cell in 1980, which look like Y-shaped structures. There are about five thousand receptors on each cell. If the antigen stuck to the macrophage isn’t recognized by the T-cell, it’s safe. But if the T-cell’s receptors match the antigen it calls in its friends.

Chemical signals are sent to call B-Cells, which create antibodies. Antibodies swim around the bloodstream and look to destroy the antigen in question. The T-cell also calls for killer T-cells which also aim to hunt down the invaders. They all divide rapidly and compose an army of four million in just a few days to ward off the sickness.

However, killer T-cells are so effective it can be detrimental to the body. The AIDS (acquired immune deficiency syndrome) virus is notably sinister because it’s one of few viruses that attacks T-cells directly. It enters T-cells and forces them to make AIDS proteins on their surfaces. So killer T-cells see the infected T-cell as a threat and kill their own kind. Since there’s only one T-cell that looks over a certain antigen if it dies nothing is left to organize a fight against the invading bodies. With the immune system destroying itself people who suffer from AIDS often die of something that is normally treatable.

Mak’s discovery of how T-cell receptors work in the immune system sheds a lot of light on the mystery of autoimmune disorders. Yet, his contributions to biochemistry don’t end there. He’s also one of the first people in the world to do studies with knock-out mice.

A knock-out mouse is a mouse that’s had one of its genes deleted, specifically one that contains instructions on creating a certain protein. Studying a mouse with one of its genes knocked-out can show what that protein did now that it’s absent. This can range from behaviour, health or physical traits.

Fruit-flies grow faster than mice, so Mak’s done a lot of research with them to figure out how to treat cancers and turn a process called apoptosis on or off. Apoptosis is programmed cell death. If a cell has bits of a virus in it, it would kill itself. Too much apoptosis can cause cell loss disorders and too little can cause uncontrolled growth, like with a cancerous tumour.

Mak now works on targeted therapeutics, which are drugs that only target diseased cells. In 1999 he found out which gene facilitates the growth of Hodgkin’s lymphoma. Knocking it out doesn’t affect the body too much so he’s hopeful this may lead to a cure for the disease, instead of the harsh chemotherapy that is currently standard practice.

By: Jassi Bedi