T Cell Therapy Shows Progress in Cancer, Infectious Diseases

Subset of T cells can confer therapeutic immune responses.

The use of T-cell therapy has shown significant progress fighting cancer and infectious diseases.

Although T cell immunity is normally able to respond to health threats and protect against recurrent diseases, they were found to become inactive or disappear in chronic diseases.

During the recent Annual Meeting of the American Association for the Advancement of Science (AAAS 2016), 3 international leaders in the field reported their latest progress.

Researchers are looking to have patients receive killer immune cells that target a diseased molecule. Although there have been multiple obstacles in the way of adopting this method into widespread clinical use, progress has been reported in all areas, including data from the first clinical trials.

These obstacles include: identifying or generating T cells that would be most effective for each individual, patient or donor; countering or avoiding any potential side effects; and finding a way to shorten the path from bench to bedside.

"There is a lot of scientific competition, of course, as well as growing industry interest," said researcher Dirk Busch. "What we bring into the game is, first, the conviction that you have to select the right cells to generate optimal cell products for therapy, together with superior techniques to do it.

“We identified a subset of T cells with high regenerative potential, where even low numbers of transferred cells -- in the extreme a single T cell -- can confer therapeutic immune responses."

At this time, the focus has been on central memory T cells (TCMs) that have the ability to engraft, expand, and live long-term even at very low numbers of transferred cells. Additionally, they can be genetically engineered to express novel antigen targeting receptors, without having an effect on their in vivo behavior.

The original clinical trials had remarkable results, including the complete remission of end-stage blood-born malignancies with the use of engineered T cells expressing chimeric antigen receptors that recognize an antigen on B cell leukemia (anti-CD19-CARs).

Success was also found in pre-clinical animal models of a potential safeguard that could selectively eliminate genetically modified T cells in therapy in the event of side effects. This mechanism has already been transferred to human patients.

“We put a marker into the T cells, so that we can give an antibody that binds to the cells that we have engineered but no others,” Busch said. “If an antibody binds to a cell, then other immune mechanisms get activated that eliminate it. We call this antibody-mediated cell toxicity. We believe the more defined our cell products are, the more predictable the clinical outcome will be.”