225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models.

ABSTRACT:

Purpose

Despite the availability of new drugs, many patients with acute myeloid leukemia (AML) do not achieve remission and outcomes remain poor. Venetoclax is a promising new therapy approved for use in combination with a hypomethylating agent or with low-dose cytarabine for the treatment of newly diagnosed older AML patients or those ineligible for intensive chemotherapy. ²²⁵ Actinium-lintuzumab (²²⁵ Ac-lintuzumab) is a clinical stage radioimmunotherapy targeting CD33 that has shown evidence of single-agent activity in relapsed/refractory AML. Increased expression of MCL-1 is a mediator of resistance to venetoclax in cancer.

Experimental design

Here we investigated the potential for ²²⁵ Ac-lintuzumab-directed DNA damage to suppress MCL-1 le

SUBMITTER: Garg R 

PROVIDER: S-EPMC7897952 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature