Grant Projects (ongoing in the year 2028)
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IHBT: Successful Commercialization of Hematology, Hematooncology and Immunotherapy Products
TQ11000057 [2024 – 2028]
The primary objective of the project is to enhance the existing infrastructure at the Institute of Hematology and Blood Transfusion (IHBT) for proof-of-concept activities aimed at testing the potential of new gene therapy drugs and modern diagnostic methods and increasing their market value in the period of project implementation. The secondary objective is to improve the economic performance of the Institute in the field of applied research and experimental development and to establish a self-sufficient system for financing technology transfer, including proof-of-concept projects in the future. The tertiary objective is the benefit of the patients of IHBT with the availability of innovative medicines and diagnostic methods in the Czech Republic. The technical parameters of these objectives are as follows: primary objective - to achieve the planned project outputs, including at least 3 modern therapeutics in clinical trials (TRL4 to TRL6), at least 4 innovative diagnostic methods (TRL4 to TRL7), at least 6 intermediate products or services supporting the innovation ecosystem in the Czech Republic in the field of modern treatments by the end of the sustainability period (target higher than TRL7). Secondary objective - to find funding mechanisms for at least 1/3 of the outputs of the sub-projects by the end of the sustainability period. Based on our experience with technology transfer, we consider these objectives to be achievable.
Single-cell analysis for deep characterization of leukemic cell subtypes responsible for aggressiveness and relapse of Ph+ leukemias
AZV NW25J-03-00098 [2025 – 2028]
Tyrosine kinase inhibitors (TKIs) targeting the oncoprotein BCR::ABL1 play a main role in the therapy of Ph+ leukemias, which significantly improved the outcome of chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (Ph+ ALL) and the overall survival of patients. However, the challenge how to prevent the progression of both diseases still remains. In Ph+ ALL, the problem is an aggressive relapse, in CML it is a progression to blast crisis, which in both cases require innovative therapeutic approaches combining TKIs with other drugs. In the proposed project, we suppose that next-generation sequencing at the single-cell level will identify leukemic cells responsible for the progression of Ph+ leukemias and that we will be able to characterize their molecular background and therapeutic targets. The aim of this project is also to distinguish lymphoblastic relapsed CML, Ph+ ALL, and Ph+ MPAL at the time of diagnosis. Methodologically, we will focus on single-cell RNA-seq with simultaneous analysis of surface markers. We will analyze cells at the time of disease relapse (for CML it will be a myeloid and/or lymphoid blast crisis) and cells from a paired sample from the time of diagnosis. To distinguish the diagnosis of Ph+ leukemias, we will analyze primary patient cells.
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.