Gene-engineered CAR T-cells and macrophages to treat Aspergillus fumigatus infection

T-cells engineered to express a chimeric antigen receptor (CAR) showed tremendous success in treating B cell malignancies. Project A8 aims to equip innate and adaptive immune cells with a CAR targeting A. fumigatus and define the optimal cell product for adoptive immunotherapy of invasive aspergillosis.

We will focus on the genetic engineering of T-cells and macrophages to direct their specificity to A. fumigatus. We will pursue three complementary and synergistic strategies to augment and fine tune the activity of A. fumigatus-specific CAR (Af-CAR) T-cells. One strategy is to use a co-receptor to enhance reactivity and selectivity of Af-CAR T-cells. Another strategy is to express an inducible IL-12 reporter gene in Af-CAR T-cells to augment the recruitment and activation of innate immune cells. In parallel, the anti-fungal activity of macrophages that are equipped with the Af-CAR will be evaluated alone and in combination with Af-CAR T-cells.