Grant Projects (ongoing in the year 2029)

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]

MUDr. Jan Vydra, Ph.D.

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.