Background Kit-M, the combination of response-modifiers GM-CSF+ Prostaglandine (PGE)1, converts myeloid blasts into dendritic cells(DC) of leukemic origin (DC_leu), that activate immune-cells against leukemia. Kit M treatment may be an attractive tool for immunotherapy in myeloid leukemia.

Materials and methods EX-VIVO: Culture of leukemic whole-blood (WB) with Kit-M, followed by ‘mixed lymphocyte culture’ (MLC) with patients’ T-cells and (functional) assays (flowcytometry, degranulation-, intracellular cytokine- and cytotoxicity assays. Correlation-analyses.

IN VIVO: treatment of leukemically diseased rats or therapy-refractory patient with Kit M, followed by immune-, hematological and clinical monitoring

Results 1. ex vivo : Treatment of 65 leukemic WB-samples with KIT-M increases frequencies of mature DC/DC_leu, reduces tolerogenic DC. Kit-M treated WB increases frequencies of (leukemia-specific) cells of the adaptive and innate immunesystem (incl. (TCRγδ,Tβ7), memory cells (Tcm,Tβ7cm)- , NKβ7,CIKβ7cells), decreases immune-suppressive T-cells (Treg4/8) and improves blast lysis after MLC. Blast-lysis correlates with frequencies of DC and leukemia-specific cells, but not with patients’ age/sex/ELN-risk/response to chemotherapy

2. In vivo - rats: Kit-M treatment of 3 leukemically diseased (vs control) rats (followed by sacrification after treatment) leads to reduced blasts and Tregs in blood and spleen and increased DC_leu and memory-like T cells.

3.In vivo - human: Kit-M salvage treatment of a 72 yo refractory AML-patient was well tolerated and the patient improved clinically (PB-blasts were below detection threshold, Neutrophils increased from 10% to 50%, thrombocytes normalized). Immune-monitoring showed a continuous activation of adaptive and innate (IFNγ producing) cells increase (incl. iNKT- , TH1/17-, B_mem-cells and DC) in PB. The patient was discharged in good clinical after the 4-weeks-therapy, however relapsed 2 weeks later.

Conclusions Kit-MTreatment of leukemic WB ex-vivo or of leukemically diseased rats or a patient in-vivo leads to (leukemia specific) activation of the adaptive and innate immune reactive cells (and downregulated suppressive mechanisms) via a DC/DC_leu triggered mechanism - resulting in significantly improved blast-lysis compared to controls (independent of patients‘ characteristics). In-vivo treatment was well tolerated, led to an increase of platelets and granulocytes and stable (low) blast counts in PB - probably mediated by a (leukemia specifically) DC/DC_leu activated immune system. A dose defining clinical trial in carefully selected patients to confirm clinical safety and efficacy is being prepared.

Disclosure Information H.M. Schmetzer: E. Ownership Interest (stock, stock options, patent or other intellectual property); Significant; Modiblast Pharma GmbH. D. Amberger: None. L. Klauer: None. E. Rackl: None. M. Atzler: None. S. Ugur: None. C. Plett: None. A. Rabe: None. C. Kugler: None. A. Rank: None. T. Baudrexler: None. M. Inngjerdingen: None. B. Eiz-Vesper: None. C. Schmid: None.