A PBD-dimer containing antibody drug conjugate targeting CCRL2 for high-risk MDS/AML including TP53-mutated disease - PubMed

3 hours ago

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.

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