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December 8, 2025BloodOpen Access

PARP1 inhibition sensitizes AML to CD123 CAR-NK cells via immunophenotypic remodeling

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Authors

SRShalini RamachandranASAnna StangerFGF Gierschek

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Overview

In vitro experiments show that PARP1 inhibition improves cytotoxicity of CD123 CAR-NK cells against leukemic stem cells, suggesting a strategy to overcome immune escape.

Key Points

  • This research aims to evaluate the combination of PARP1 inhibition with CD123 CAR-NK cell therapy in targeting acute myeloid leukemia.
  • Generated CD123 CAR-NK cells from healthy donor NK cells via lentiviral transduction.
  • Performed cytotoxicity assays on AML cell lines and primary samples with and without PARP1i pre-treatment.
  • Used flow cytometry and CFU assays to analyze residual populations and clonogenic potential in vitro.
  • Implemented a patient-derived xenograft model in NSG mice to assess in vivo efficacy of CAR-NK cell therapy with PARP1i.
  • CD123 CAR-NK cells showed strong antigen-specific killing in vitro, particularly against CD123high AML cells.
  • In vivo, significant reductions in leukemic burden were observed in peripheral blood, spleen, and liver following CAR-NK cell treatment.
  • PARP1 inhibition enhanced killing efficacy of CAR-NK cells by improving immunophenotype for NK cell recognition.
  • Clonogenic potential of AML cells was reduced by 8-fold with the combination therapy compared to untreated samples.

Cite This Study

Ramachandran et al. (2025) studied this question.

synapsesocial.com/papers/69362f694fa91c937236dee7https://doi.org/10.1182/blood-2025-2357
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effiefficacy and safety of allogeneic CD123 CAR-NK cell therapy in Relapsed/Refractory Acute Myeloid Leukemia2025 · 3 citations
  2. 2Abstract P20: Anti-CD123 CAR NK cells and cam161533 Trispecific Killer Engager have synergistic activity against Acute Myeloid Leukemia2024 · 1 citations
  3. 3Abstract 1327: Affinity tuning anti-CD123 chimeric antigen receptor natural killer cell therapy to treat acute myeloid leukemia2024
  4. 4Abstract 5199: uPAR-targeting CAR-NK cells enhance cytotoxicity against acute myeloid leukemia2026
  5. 5A phase 1 trial of CD123-directed chimeric antigen receptor T-cell therapy in adults with relapsed/refractory acute myeloid leukemia or blastic plasmacytoid dendritic cell neoplasm2026