Grant Projects (ongoing in the year 2029)
View ongoing grants in the year: 2009, 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023, 2024, 2025, 2026, 2027, 2028, 2029, 2030.
Safety and efficacy of anti-CD123 chimeric antigen receptor-modified autologous T cells (CART123) in patients with relapsed/refractory CD123+ hematologic malignancies.
NW26-03-00535 [2026 – 2029]
Treatment with genetically modified T lymphocytes expressing a chimeric antigen receptor (CAR) is a highly innovative approach to cancer therapy. Currently, this treatment is available for CD19 and BCMAA positive malignancies. At IHBT, previous projects successfully developed CAR targeting the CD123 antigen, which is expressed in most cases of acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and some cases of advanced myelodysplastic syndrome (MDS) and ALL. An innovative method for manufacturing autologous CAR-T cells containing anti-CD123 CAR (CART123) under GMP conditions was established and validated, utilizing non-viral transduction of linear DNA. Preclinical trials were successfully conducted, and clinical trial was approved and initiated. The subject of the proposed project is a Phase I clinical trial (CT) of CART123 in patients with refractory or relapsed CD123-positive AML, MDS, ALL, or BPDCN. This is an open-label, dose-escalation trial in three cohorts, using a Bayesian Optimal Interval (BOIN) approach to optimize the process of determining the maximum tolerated dose (MTD). The primary objectives of the study are to assess the safety of CART123, evaluate hematopoietic recovery, and determine the appropriate dose for further research based on MTD assessment. The secondary objectives include evaluating efficacy and the feasibility of subsequent allogeneic hematopoietic transplantation. In addition to clinical outcomes, correlative analyses of CART123 phenotype and persistence will be conducted using flow cytometry, histology, immunohistochemistry, and molecular genetic methods. Up to 18 evaluable patients will be enrolled in the clinical trial, depending on the occurrence of dose-limiting adverse events assessed by an independent DSMB committee. The proposal builds on the results of the preclinical projects AZV NU23-03-00188 and AZV NU22-05-00374, whose principal investigator is part of the project team.
Identification of therapeutically targetable mechanisms in adult patients with difficult-to-treat acute lymphoblastic leukemia
AZV NW27-03-00520 [2027 – 2030]
doc. MUDr. Cyril Šálek, Ph.D.
MUDr. Štěpán Hrabovský, Ph.D., FN Brno
Acute lymphoblastic leukemia (ALL) in adults remains a high-risk malignancy, particularly in patients with T-cell ALL (T-ALL) and relapsed/refractory (R/R) B-cell precursor ALL (B-ALL), where treatment failure and relapse are frequent. Despite advances in risk-adapted therapy and immunotherapy, the molecular mechanisms driving resistance and disease progression remain insufficiently understood, and clinically actionable targets are limited. This project aims to identify therapeutically targetable mechanisms in high-risk ALL by combining detailed molecular characterization of leukemic cells with functional testing of drug response. We will analyze samples obtained at diagnosis and relapse using whole-exome sequencing, wholetranscriptome sequencing, digital MLPA, and Nanopore whole-genome sequencing to detect gene mutations, gene fusions, copy number alterations, and transcriptional changes associated with treatment failure and clonal evolution. Functional relevance of identified alterations will be assessed by ex vivo drug sensitivity testing on primary leukemic cells and by apoptosis signaling analyses at the single-cell level. Promising therapeutic approaches will be further validated in patient-derived xenograft (PDX) models. In parallel, we will investigate how tyrosine kinase inhibitors affect leukemic cell signaling, metabolism, and interaction with immune effector cells, with emphasis on their impact on T-cell–mediated cytotoxicity. The project builds on established national collaboration and preliminary data demonstrating feasibility of integrated genomic and functional analyses. Expected outcomes include identification of biomarkers predictive of treatment response, improved classification of high-risk ALL, and validation of rational targeted treatment strategies. The project will support implementation of precision diagnostics and therapy, ultimately improving outcomes of adult patients with aggressive ALL.
Biological Characterization of Myelodysplastic Syndrome in Younger Adults: Genetic Predisposition, Clonal Architecture, and Inflammatory Profile with Implications for Diagnosis and Treatment
AZV NW27-07—00184 [2027 – 2030]
Doc. RNDr. Monika Beličková, Ph.D., MHA
MUDr. Petra Bělohlávková, Ph.D., FN Hradec králové, MUDr. Libor Červinek, Ph.D., FN Brno, doc. RNDr. Zuzana Zemanová, CSc., VFN Praha
Myelodysplastic syndromes (MDS) are predominantly diseases of older age; however, in younger adults they represent a relatively rare but important subgroup, with more frequent indication for curative allogeneic transplantation and a possible hereditary background. The project is designed as a multicenter observational study in the Czech Republic within the Czech MDS Group, with retrospective and prospective components. The primary cohort will consist of patients newly diagnosed with MDS at age
Advanced Preclinícal Platform for Evaluation and Personalization of NK Cell Immunotherapies (ADVANCE-NK)
AZV NW27-03-00106 [2027 – 2030]
Mgr. Jan Frič, Ph.D., MHA
Mgr. Marcela Hortová Kohoutková, Ph.D., FNUSA Brno
Acute myeloid leukemia (AML) remains a high-risk hematological malignancy with poor outcomes, particularly in relapsed or refractory disease, where survival remains limited despite recent therapeutic advances. In contrast to B-cell malignancies, AML lacks a universally targetable antigen, restricting the applicability of current immunotherapies and underscoring the need for alternative strategies. Natural killer (NK) cell-based immunotherapy offers a promising solution due to its antigen-independent cytotoxicity, favorable safety profile, and suitability for allogeneic “off-the-shelf’ use. However, its clinical translation is limited by donor-dependent variability in expansion and function, suboptimal manufacturing consistency, and the absence of predictive preclinical models that reflect the leukemia microenvironment. The ADVANCE-NK project aims to establish a preclinical platform for the evaluation and personalization of NK cell immunotherapies in AML. Building on preliminary data, the project combines optimized CGMP-compatible expansion of NK cells from umbilical cord blood, predictive profiling for donor selection, and advanced 3D bone marrow organoid models that recapitulate key features of the leukemic niche. The project will validate transcriptomic signatures predictive of NK-cell proliferation and cytotoxicity and translate them into a rapid qPCR-based assay for quality control. In parallel, genetically engineered NK-cell products, including CXCR4-expressing cells to enhance bone marrow homing and CD123-targeted CAR-NK cells to improve antileukemic activity, will be developed and functionally tested. Using advanced 3D models, the platform will enable physiologically relevant assessment of NK-cell migration, persistence, and cytotoxicity, supporting personalized matching of NK-cell products to patient-specific AML targets. This strategy is expected to improve therapeutic efficacy, reduce production variability, and accelerate clinical translation.