| Autor: |
Lu, Hua, Zhou, Quan, Deshmukh, Vishal, Phull, Hardeep, Ma, Jennifer, Tardif, Virginie, Naik, Rahul R., Bouvard, Claire, Zhang, Yong, Choi, Seihyun, Lawson, Brian R., Zhu, Shoutian, Kim, Chan Hyuk, Schultz, Peter G. |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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