Treating aspergillosis, in this case, acute invasive aspergillosis, with antifungal medication has its limitations. They tend to be quite toxic and have to be used carefully by experienced medical practitioners. When treating a severely immunocompromised person infected with Aspergillus (which is the main group of people that get the acute invasive form of this disease) mortality rates can exceed 50% in patient groups being treated for leukemia. It is easy to see that we need to develop better treatments and different treatment strategies.
A German research group at the University of Wurtzburg, led by Jurgan Loffler and Michael Hudacek has adopted a completely different approach to treating aspergillosis, instead of developing antifungal medication they have opted to ‘train’ the immune system of immunocompromised patients to recognise and attack the infection better in the hope that this will improve mortality.
This technology has been copied from cancer research, where we know that some cancers escape attack from the host’s immune system and this allows cancer to grow. Researchers are successfully ‘retraining’ the host’s immune system to attack the cancer cells more effectively.
The group took cells from a mouse’s immune system (T-cells) that normally attack infecting microbes in order to eliminate infections and boosted their ability to find Aspergillus fumigatus, which is the main pathogen that causes aspergillosis. These cells were then given to mice infected with Aspergillus a mouse model system intended to simulate acute invasive aspergillosis in human patients.
The result was that of those mice that had invasive pulmonary aspergillosis and had no treatment, 33% remained alive whereas for those mice that were treated with the booster T-cells (CAR-T) 80% survived.
This result shows much promise for the treatment of aspergillosis. These experimental results need to be repeated in a human host but it is clear that this approach could form the basis for an entirely new way to treat aspergillosis, including the chronic forms of aspergillosis such as chronic pulmonary aspergillosis (CPA) and maybe even allergic bronchopulmonary aspergillosis (ABPA).