The cultivated anti-R. oryzae T cells proliferate upon restimulation with R. oryzae antigens and increase the oxidative burst C646 molecular weight activity of both granulocytes and monocytes, indicating that the anti-R. oryzae T cells increase the antifungal activity of phagocytes. In addition, the generated T cells exhibit cross reactivity to other mucormycetes such as Rhizopus microsporus, Rhizomucor pussilus and Mucor circinelloides, but unfortunately, no activity against all fungi tested could be observed. As the immunological relevant antigens of the different fungi are poorly characterised, molecularly engineered T cells targeting specific fungal antigens

are lacking to date, but would be a major progress in adoptive antifungal immunotherapy. Adoptive immunotherapy transferring allogeneic T cells is always associated with the risk of the induction of graft-vs.-host disease (GvHD), as donor-derived T cells may recognise and attack normal tissues of the recipient as ‘foreign’. GvHD can affect skin, liver, gut and is potentially lethal. The pathophysiology of GvHD is complex and includes proliferation of T cells and the production of inflammatory

cytokines. Our in vitro experiments demonstrated that compared to unselected T cells, the generated anti-R. oryzae T cells exhibit selleck inhibitor both lower proliferation and lower IFN-γ production when co-incubated with third-party antigen-presenting cells, both of which indicates a loss of alloreactive potential in vitro. Although the incidence of mucormycosis seems to increase, to date, the incidence of invasive aspergillosis is significantly higher than mucormycosis.[1, 14] Unfortunately, in most patients with suspected invasive fungal disease, the causative agents of both diseases are rarely isolated and identified, which is a prerequisite for implementation

of adoptive immunotherapy with specific antifungal T cells. In addition, a substantial number of patients are co-infected with fungi of different species or genera.[1, 14] This was the rationale to develop a rapid and feasible strategy to generate TH1 cells which target a multitude of different clinical important fungi.[19] We could generate multipathogen-specific antifungal T cells BCKDHA using a combination of cellular extracts of Aspergillus fumigatus, Candida albicans and R. oryzae. The generated cells were characterised as activated memory T cells of the TH1 type, which respond to a multitude of Aspergillus species, Candida species and mucormycetes, although the cells do not respond to all medical important fungi. The supernatant of the restimulated multispecific antifungal T cells significantly enhances the activity of granulocytes, independently whether the T cells were stimulated with naturally processed antigens of A. fumigatus alone, C. albicans alone, R. oryzae alone or of all three fungal pathogens together respectively.