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.
|Seif M, Kakoschke TK, Ebel F, Bellet MM, Trinks N, Renga G, Pariano M, Romani L, Tappe B, Espie D, Donnadieu E, Hünniger K, Häder A, Sauer M, Damotte D, Alifano M, White PL, Backx M, Nerreter T, Machwirth M, Kurzai O, Prommersberger S, Einsele H, Hudecek M, Löffler J||2022||CAR T cells targeting Aspergillus fumigatus are effective at treating invasive pulmonary aspergillosis in preclinical models.||Science Transl Med 14: 664||Sciene Transl Med|