T-cells: cancer’s newest enemies

BY Richard C. Koya, M.D., Ph.D.

Cancer is an ominous disease, which can spread beyond possible control even with the best available treatments.

Currently, doctors can still surgically remove it, poison it with drugs via chemotherapy, or with radiation damage through radiotherapy.

But our body’s immune system, which evolved to protect us against germs and other foreign invaders, could be harnessed to direct its destructive power toward its own cells gone dangerously mad, i.e., the cancer cells.

The question is how to teach our defense system to recognize these previously law-abiding citizens turned rebellious terrorists.

Enter the T-cell receptors. These are the sensing machines that are present on the surface of T-cells, a specialized deadly soldier from the white blood cell army, that can specifically detect the ID tags exposed by the genes of each cell.

And by utilizing gene therapy approaches, we can now engineer these T-cells in an efficient way, inserting new T-cell receptors that recognize cancer cells.

The key is to find a good target ID tag (present in tumor, but not in normal cells) and an even better matching T-cell receptor.

Likewise, we should also be able to tag T-cells so we can track how these new re-programmed soldiers are performing.

Using the aggressive skin cancer melanoma as a model, we engineered T-cells harvested from special transgenic mice that have human derived genes.

In this way, all the findings from this model could be directly used to design clinical trials with real patients, shortcutting the gap between lab work and bedside care.

We were able to directly observe the T-cells fighting the cancer in the mice.

Our work was published this week in the journal Proceedings of the National Academy of Sciences. Read more in the online edition of the journal.

Koya is an assistant professor of surgical oncology at the David Geffen School of Medicine.