P07.02 Control leukemia by inducing anti-cancer immune reactivity in vivo? – Potential of a DC-triggered mechanism. (21st September 2022)

• Record Type: Journal Article
• Authors: Schmetzer, HM; Amberger, D; Klauer, L; Rackl, E; Atzler, M; Ugur, S; Plett, C; Rabe, A; Kugler, C; Rank, A; Baudrexler, T; Inngjerdingen, M; Eiz-Vesper, B; Schmid, C
• Is Part Of: Journal for immunotherapy of cancer. Volume 10(2022)Supplement 1
• Page Start: A25
• Page End: A25
• Publication Date: 2022-09-21
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2022-ITOC9.46
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Kit-M, the combination of response-modifiers GM-CSF+ Prostaglandine (PGE)1, converts myeloid blasts into dendritic cells(DC) of leukemic origin (DCleu ), 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/DCleu, 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 DCleu 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-, Bmem -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/DCleu 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/DCleu 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.