title: 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, αCLL1-αCD3, using the genetically encoded unnatural amino acid, p-acetylphenylalanine. The resulting αCLL1-αCD3 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, αCLL1-αCD3 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.
authors: Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037 (USA).
authors: Hua
authors: H
authors: Lu
authors: Quan
authors: Q
authors: Zhou
authors: Vishal
authors: V
authors: Deshmukh
authors: Hardeep
authors: H
authors: Phull
authors: Jennifer
authors: J
authors: Ma
authors: Virginie
authors: V
authors: Tardif
authors: Rahul R
authors: RR
authors: Naik
authors: Claire
authors: C
authors: Bouvard
authors: Yong
authors: Y
authors: Zhang
authors: Seihyun
authors: S
authors: Choi
authors: Brian R
authors: BR
authors: Lawson
authors: Shoutian
authors: S
authors: Zhu
authors: Chan Hyuk
authors: CH
authors: Kim
authors: Peter G
authors: PG
authors: Schultz
mesh_terms: D000328:Adult; D018033:Antibodies, Bispecific / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D037181:Lectins, C-Type / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D037181:Lectins, C-Type
keywords: CLL1; acute myeloid leukemia; bispecific antibodies; cancer immunotherapy; unnatural amino acids