16 February 2016

T-cell therapy for cancer and chronic infections

Reprogrammed immune cells will help defeat cancer and bacteria

Ivan Zagorsky, Vesti 

In recent years, doctors have associated more and more hopes in the treatment of cancer and dangerous infectious diseases with new technologies of adaptive cellular immunotherapy, when a patient is saved from imminent death with the help of altered cells or donor cells.

Encouraging results, in particular, are brought by clinical studies of receiving T-lymphocytes reprogrammed to destroy tumors or pathogenic microorganisms.

At the annual meeting of the American Association for the Advancement of Science (AAAS 2016) on the latest achievements (within the session Fighting Cancer and Chronic Infections with T Cell Therapy: Promise and Progress – VM) were reported by three world leaders in this field: Dirk Busch from the Technical University of Munich, Chiara Bonini from the San Raffaele Scientific Institute and Stanley Riddell from the Fred Hutchinson Cancer Research Center.

Usually, different types of T-lymphocytes, including T-helpers, T-killers and T-suppressors, acting together, effectively recognize and destroy the sources of the disease, forever preserving information about them for a quick reaction in case of re-infection. But in some chronic diseases, the cells of the immune system can lose their activity and even completely disappear. Recent studies show that the protective properties of T-lymphocytes can be restored and directed to the treatment of not only chronic diseases, but also cancer.

Before the start of mass clinical trials, scientists had to solve a number of problems. In particular, there was no consensus on whether to create T-lymphocytes targeted at a particular source of the disease artificially or to search for the right cells in the patient's or donor's body.

"There is a lot of competition in science, in addition, there is growing interest in the industry," says Bush. "We are convinced that we must choose the right cells to produce the optimal product using the most advanced methods. In recent years, we at the Technical University of Munich, as well as colleagues Riddell and Bonini, have been working on the creation of cellular products that, after transplantation to a patient, multiply rapidly and remain active for a long time, potentially throughout life. We have identified a type of T-cells with a high regenerative potential that can trigger an immune response even when transplanting a small number of such cells. Perhaps only one lymphocyte will be enough for this."

Recall that one lymphocyte can transmit information about the violator to fellow cells (provided that he does not die before that). Accordingly, he can also "tell" others about an enemy that other immune cells in this body have not previously met.

The use of such "capable" cells requires special guarantees of the safety of the method, but according to scientists, they managed to prove this.

The group focused on memory T cells, which survive and multiply better than others during transplantation. In addition, with the help of genetic engineering methods, genes responsible for the work of new receptors can be "included" in them. These kind of "attack sensors" can target pathogens they haven't encountered in the past.

In the first clinical studies, modified T cells were used, producing so-called chimeric antigen receptors that recognize leukemia-affected B lymphocytes. As a result, the patient's own immunity, being set against the enemy, destroys the disease itself.

Scientists have received good results, and in some cases, the transplant helped to completely cure the patient at the terminal (final before death) stage of leukemia, stopped the spread of malignant tumors. The new therapy has proven itself well in other studies aimed at chronic infectious diseases.

The researchers also demonstrated a method that allows selectively removing transplanted T cells from the body in case of side effects. This "safety system" has been successfully tested on animals and is already being used to protect people from the undesirable effects of therapy.

"We put a marker on our T-lymphocytes, and subsequently we can introduce an antibody that will only bind to our cells," Bush explains in a press release "Immunotherapy: Technical innovations from TUM could help bring cures within reach." "After that, another immune mechanism is triggered, which destroys the transplanted cells."

Technologies developed by a team of specialists have already found business support in the face of a large American company Juno Therapeutics.

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