KK2845, a PBD dimer-containing antibody-drug conjugate targeting TIM-3-expressing AML.

ABSTRACT: Acute myeloid leukemia (AML) is a common hematopoietic malignancy with high recurrence rates, and there is an urgent need for new therapeutic agents. T-cell immunoglobulin mucin-3 (TIM-3) is expressed on the surface of both LSCs and blasts in most AML patients, but not in normal hematopoietic stem cells (HSCs). We have developed KK2845, an antibody drug conjugate (ADC) that consists of an anti-TIM-3 fully human IgG1 antibody, a valine-alanine linker and a highly potent DNA cross-linking pyrrolobenzodiazepine (PBD) dimer SG3199. KK2845 exhibited potent cytotoxicity against AML cells both in vitro and in vivo. The cytotoxicity against AML cells was almost comparable between KK2845 and CD33-ADC, an anti-CD33 antibody conjugated with PBD dimer that has shown high remission rates in clinical st

SUBMITTER: Zou J 

PROVIDER: S-EPMC12310520 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature