Study on T cells may lead to better cancer drugs

Study on T cells may lead to better cancer drugs

A study focused on invariant natural killer T (iNKT) cells and how they are activated could lead to better cancer drugs and even vaccines against the disease, scientists believe.

Despite iNKY cells being relatively rare in human blood - comprising less than one per cent of peripheral blood mononuclear cells - they are vital because they can bring about an array of polarised immune responses.

The cells exist in a poised effector state until activation, whereupon they produce cytokines to fight foreign lipid antigens.

It has long been suspected that finding new ways to spark these cells into action could have important consequences for oncology research, but studies so far have only been able to produce promising responses in mice.

For this research, a team led by University of Connecticut chemistry professor Amy Howell used a new compound called AH10-7 that was a modified version of an earlier synthesized ligand.

Glycolipid ligands, or α-GalCers, are potent activators of iNKT cells and so the team added a hydrocinnamoyl ester to stabilise it and also keep it close to the surface of the antigen-presenting cell.

This meant its ability to dock with and stimulate iNKT was greatly increased. Furthermore, the researchers trimmed off part of the base to initiate a critical Th1 cytokine bias, which is crucial for anti-tumour immunity. Both of these factors were able to strengthen the efficacy of the entire molecular complex in terms of iNKT activation.

Writing in the journal Cell Chemical Biology, the scientists explained that the new compound gets around the issues of earlier varieties, which often generated a rush of different cytokines that sometimes worked against each other, because of its unique chemical structure.

It is hoped that this insight into what is happening at the molecular level of an immune response will generate new leads for research and could also lead to more effective compounds being developed for cancer treatment.

Study co-author Jose Gascon said: "We are providing protocols so that other scientists can rationally design related molecules that elicit desired responses from iNKT cells."