LONDON – It may be possible to develop a new type of immunotherapy that could efficiently eliminate all types of cancer cells, a new study suggests.

The research, led by scientists at the University of Freiburg in Germany, found that stimulating a particular type of T cell with a monoclonal antibody turned the cells into highly effective killers. When the researchers added these stimulated T cells to cancer cells in the laboratory, all the cancer cells died within four hours.

Wolfgang Schamel, professor of immunology at the University of Freiburg, told BioWorld Today, "With conventional protocols, not all the cells are killed in these types of experiments, and it takes longer. But we repeated these experiments many times and each time we obtained a huge effect. This work opens up the possibility of developing an enormously enhanced form of immunotherapy against most, if not all, forms of cancer."

Schamel and his colleagues reported their findings in the May 22, 2014, edition of Cell Reports, in a paper, titled "The CD3 conformational change in the γδ T cell receptor is not triggered by antigens, but can be enforced to enhance tumor killing." The first author is Elaine Dopfer.

The study began with an exploration of the receptors present on T cells. There are two classes of T cells, αβ T cells and γδ T cells. The αβ T cells, which are more abundant than the γδ T cells, are able to recognize foreign proteins, including those deriving from microorganisms and those present on tumor cells.

In the past, researchers have tried to develop cancer therapies by encouraging αβ T cells to kill cancer cells, but this has not been very effective because the T cells will only recognize a specific mutation, and this will vary from patient to patient (and presumably among different tumor cells within the same patient, too).

By contrast, γδ T cells, of the type known as Vγ9Vδ2, are able to recognize cancer cells because they can detect metabolites that are specific to cancer cells. (All cancer cells produce energy using glycolysis, rather than by oxidative phosphorylation.) The γδ T cells therefore play a key role in immunosurveillance identifying and eliminating any tumor cells that develop.

For this reason, Schamel and his team were interested in understanding more about the γδ T cell receptor on these T cells.

"We wanted to know more about this receptor: how it works and how the different components come together to form a complex, and so on," Schamel said. "Then, by pure chance, my PhD student, Elaine Dopfer, found that when she let a certain monoclonal antibody bind to the γδ receptor, it induced a conformational change. This was odd, because this conformational change normally only occurs in the receptor on the αβ cells."

The finding was very surprising, he added, because the two receptors seemed very similar and the researchers would never have guessed that they worked in different ways.

The team went on to look at the consequences for the function of the γδ T cells.

"Our experiments showed that if we induced this conformational change in these cells, they proliferated less and produced lower levels of cytokines," Schamel said. "This seemed to make sense, that this conformational change would not normally happen, because it seemed to have an inhibitory effect on their function."

What they saw next came as a big surprise. Collaborating with the clinical team headed by professor Dieter Kabelitz at the University of Kiel in Germany, they then found that the ability of the stimulated γδ T cells was "enormously enhanced," Schamel said. "This is a very interesting finding for clinicians, because, to work as a therapy, you want the cells to kill tumors, but you don't want to potentiate cytokine production. In the worst case scenario, you could precipitate a cytokine storm. Yet here we have enhanced tumor killing, while minimizing release of cytokines."

Schamel is currently applying for research grants and seeking clinical collaborators, in order to take the work to the next level. "We want to begin animal experiments using mouse models of human cancers, to find out if we get the same benefit in a living organism as we saw in our petri dishes," he said. "This work provides us with a novel and detailed insight into how the T cell receptors work on these γδ T cells, and it has huge potential in terms of translational application into the clinical setting."