ITOC2 – 014. Immunomodulation of blasts in AML-patients (AML-pts) with clinically approved response modifiers to improve antileukemic T-cell reactivity: An ex vivo simulation of the clinical

Abstract

Antileukemic T-cell-reactivity has to be improved in AML-pts. Leukaemia-derived DC (DCleu) are most effective antileukemic T-cell-stimulators. We tested combinations of clinically approved immune modifiers to convert blasts into a ‘DCleu-vaccine', that induces antileukemic T-cell (memory) without induction of blast proliferation in 52 AML-samples. 11 KITS with combinations of seven clinically approved compounds (GMCSF, INTRON, CALCIMYCIN, PICIBANIL, PGE1,2, TNF<i>α</i>) tested in Whole Blood (‘WB') culture system to generate DCleu, to induce (unwanted) blast proliferation and to stimulate antileukemic activity of pts' T-cells. 1. Generation of DC, DCleu from WB: seven of 11 Kits produced DCleu comparable to standard methods. 2. Some KITS induced ex vivo blast proliferation in individual pts' WB. 3. Best five of 11 blast modulating KITs evaluated by ranking. 4. Antileukemic reactivity of T-cells stimulated with KIT-treated WB was improved compared to controls. 5. Blast lysis correlated with proportions of DC-subtypes (DC, DCleu), CD8+ Tcells after mixed lymphocyte culture and concentrations of IL-12, IFNg, IL-6 and −8 in culture supernatants. <i>Conclusion:</i> KITs can create DCleu from blasts in WB cultures. Blast-stimulating potential and capacity to generate antileukemic T-cells can be evaluated. A ranking based on DC, DCleu subtypes, antileukemic reactivity and cytokine profiles should be created to allow an individualised selection of, best KIT' for <i>in vivo</i> applications. (Patent pending).