Stimulation with lysates of @entity13473 , Candida krusei and XXXX maximizes cross-reactivity of anti-fungal T cells.

@entity1 @entity7144 @entity1619 @entity13473 @entity364 @entity54 @entity375
BACKGROUND AIMS:    Invasive @entity364 caused by filamentous fungi and @entity375 are significant causes of morbidity and mortality in immunosuppressed hematology @entity1 . We previously published a method to expand @entity54 -specific T cells for clinical cell therapy. In the present study, we investigated expansion of T cells specific for other fungal pathogens and creation of a broadly reactive @entity1619 -cell product. METHODS:    Fungal strains selected were those frequently observed in the clinical hematology setting and included @entity54 , Candida, Fusarium, Rhizopus and Lomentospora/Scedosporium. Four T-cell cultures specific to each fungus were established. We selected lysates of @entity13473 , Candida krusei and @entity7144 to expand @entity1619 cells. Allelic restriction of anti-fungal activity was determined through the use of specific major histocompatibility complex class II-blocking antibodies. RESULTS:    Individual T-cell cultures specific to each fungus could be expanded in vitro, generating predominantly CD4(+) T cells of which 8% to 20% were fungus-specific. We successfully expanded @entity1619 cells from the peripheral blood (n   =   8) and granulocyte-colony-stimulating factor-primed stem cell products (n   =   3) of normal donors by using a combination of lysates from @entity13473 , Candida krusei and Rhizopus oryzae. Anti-fungal activity was mediated through human leukocyte antigen (HLA)-DR alleles and was maintained when antigen-presenting cells from partially HLA-DRB1-matched donors were used to stimulate T cells. CONCLUSIONS:    We demonstrate a method to manufacture @entity1619 -cell products with specificity against a range of clinical fungal pathogens by use of the blood and stem cells of healthy donors as the starting material. The safety and efficacy of these products will need to be tested clinically.
