Immunotherapy: Memory T cells to protect against infection

Cell products are prepared in special clean room facilities

© © TUM/Michael Neuenhahn

In a clinical trial at the German Center for Infection Research (DZIF), leukaemia patients are being administered specially purified immune cells, so-called memory T cells, for the first time after a bone marrow transplant. These special immune cells are to protect the patients against infection until their own immune defence functions. This is a “proof of concept” trial, designed to test a method that could also be applied to other diseases.

“First and foremost, this trial is to help patients suffering from severe leukaemia who can only be cured with a bone marrow transplant,” explains Dr Michael Neuenhahn from the TU München. Together with Prof Dirk Busch, also from TU München, he is heading this clinical phase I/II trial in which the first patient has been treated recently. Normally, patients who have had a bone marrow transplant are at great risk: their immune system which has been suppressed together with the degenerate cells, needs time to regenerate which can take up to a year. Infectious pathogens can take advantage of this immunosuppression and cause severe illness. Examples are herpes viruses like the cytomegalovirus and Epstein-Barr virus. In order to avoid such complications, the scientists prophylactically administered small amounts of specially prepared memory T cells. These cells are often able to identify infectious disease pathogens and defend against them.

“In this current trial, these specially purified memory T cells, subgroups of T lymphocytes, have been administered in this form for the first time in the world,” explains Dirk Busch. Over the last years, together with the company JUNO, the scientist developed an innovative cell purification method with which the desired cells can very specifically be isolated from healthy donor blood. In many preliminary tests the scientists could demonstrate that especially these particular cells can protect against infection in very small, well-tolerated doses. This is a major advantage because T cells can be both a blessing and a curse. If they are administered to a patient unfiltered in too high amounts, they can cause rejection reactions in which the T cells also attack healthy cells. However, if they are not at all present, the dreaded infectious disease pathogens can multiply.

“Our aim is to decrease the risk of infection without risking rejection reactions,” explains Neuenhahn and, after all the preliminary testing, he is optimistic that this will work. Over the course of one year, 30 leukaemia patients are to receive this T cell prophylaxis. In each case, the dosage will be incremented gradually so as to identify the optimal dose. The patients will be examined for infections in closely meshed time intervals. The cell purification will take place in special clean room facilities in Munich. Trial patients can be treated in Würzburg as well as at the DZIF partner sites Tübingen and Hannover.

This trial is a good example of successful translation at the DZIF. For the first time, developments from basic research have been realised all the way through to a cell product that the patient benefits from. “We are highly convinced that these memory T cells work,” says Dirk Busch. They protect against a whole range of pathogens. For Busch, this is a “proof of concept” trial which could subsequently open up the method to broader clinical application. “On the one hand, it could be used as infection prophylaxis for other organ transplants and situations in which patients have weakened immune systems. On the other hand, this technology will, in future, also make cell manipulation possible, so that these cells can specifically target cancer cells.

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