Engineered T-cell treatment helps keep cancer at bay

Cancer has been winning the arms race agains the immune system for too long, but scientists are developing plenty of new weapons to try to turn the tide. One key technique is to supercharge T-cells – the foot-soldiers of the immune system – to better detect and kill tumors, and a new trial at the Children's Research Institute has delivered promising results, keeping cases of Hodgkin's lymphoma at bay for years at a time. 

Normally, T-cells protect us from infection by patrolling the body, seeking out specific protein signatures that indicate invading bacteria, viruses or cancer cells, and then rallying more T-cells together to attack the threat. At least, that's how it would work in a perfect world. In our imperfect world, tumors have developed workarounds that ensure their survival.

A signaling protein known as transforming growth factor beta (TGF-beta) usually controls the growth of healthy cells, but tumors have TGF-beta mutations that allow the cancer to spread to neighboring cells. At the same time, excess TGF-beta can deactivate attacking T-cells, allowing the tumor to avoid detection by the immune system.

To counter that defense mechanism, the team at the Children's Research Institute engineered a new type of T-cell. The researchers modified LMP-specific T-cells (LSTs) to express a dominant-negative TGF-beta receptor type 2 (DNRII). The resulting T-cells were called DNRII-LSTs, and they were designed specifically to fight Epstein Barr virus-positive Hodgkin's lymphoma.

By expressing DNRII, the engineered T-cells are able to survive in the hostile environment around the tumor and continue their usual seek-and-destroy mission. In this case, they would target proteins associated with the Epstein Barr virus, which the tumors would express.