A PBD-dimer containing antibody drug conjugate targeting CCRL2 for high-risk MDS/AML including TP53-mutated disease - PubMed
4 hours ago
- #MDS/AML
- #CCRL2-targeting ADC
- #TP53-mutated
- Patients with high-risk MDS/AML, especially TP53-mutated cases, have poor outcomes due to lack of effective therapies.
- CCRL2 is overexpressed in MDS/sAML, with highest levels in TP53-mutated and erythroid-feature subtypes.
- An anti-CCRL2 ADC conjugated with a PBD-dimer induced strong, selective cytotoxicity against TP53-mutated MDS/AML cell lines, outperforming gemtuzumab and other ADCs.
- The ADC induced apoptosis and suppressed clonogenicity in primary MDS/AML samples without harming healthy hematopoietic cells.
- In xenograft models, the ADC suppressed leukemic growth, improved survival, and reduced leukemic burden in TP53-mutated MDS/AML.
- The study identifies CCRL2 as a promising new therapeutic target for high-risk MDS/AML, including TP53-mutated disease.