Targeting human C-type lectin-like molecule-1 (CLL1) with a bispecific antibody for immunotherapy of acute myeloid leukemia.

ABSTRACT: Acute myeloid leukemia (AML), which is the most common acute adult leukemia and the second most common pediatric leukemia, still has a poor prognosis. Human C-type lectin-like molecule-1 (CLL1) is a recently identified myeloid lineage restricted cell surface marker, which is overexpressed in over 90% of AML patient myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a novel bispecific antibody, ?CLL1-?CD3, using the genetically encoded unnatural amino acid, p-acetylphenylalanine. The resulting ?CLL1-?CD3 recruits cytotoxic T?cells to CLL1 positive cells, and demonstrates potent and selective cytotoxicity against several human AML cell lines and primary AML patient derived cells in?vitro. Moreover, ?CLL1-?CD3 treatment completely eliminates established tumors in an U937 AML cell line xenograft model. These results validate the clinical potential of CLL1 as an AML-specific antigen for the generation of a novel immunotherapeutic for AML.

SUBMITTER: Lu H 

PROVIDER: S-EPMC4280064 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature