Abstract：
:TAM family members (TYRO3, AXL and MERTK) play essential roles in the resolution of inflammation and in infectious diseases and cancer. AXL, a tyrosine kinase receptor, is commonly overexpressed in several solid tumours and numerous hematopoietic malignancies including acute myeloid leukaemia, acute lymphocytic leukaemia, chronic myeloid leukaemia, chronic lymphocytic leukaemia and multiple myeloma. AXL significantly promotes tumour cell migration, invasion and metastasis, as well as angiogenesis. AXL also plays an important role in inflammation and macrophage ontogeny. Recent studies have revealed that AXL contributes to leukaemic phenotypes through activation of oncogenic signalling pathways that lead to increased cell migration and proliferation. To evaluate the mechanisms underlying the role of AXL signalling in tumour metastasis, we screened a phage display library to generate a novel human monoclonal antibody, named DAXL-88, that recognizes both human and murine AXL. The concentrations of DAXL-88 required for 50% maximal binding to human and murine AXL were 0.118 and 0.164 μg/mL, respectively. Furthermore, DAXL-88 bound to human AXL with high affinity (KD ~ 370 pM). DAXL-88 blocked the interaction between AXL and its ligand, growth arrest-specific gene 6 (GAS6), with a half maximal inhibitory concentration of 2.16 μg/mL. Moreover, DAXL-88 inhibited AXL/GAS6-dependent cell signalling, which is implicated in cell migration and invasion. In conclusion, the novel anti-AXL DAXL-88 high-affinity antibody blocks the interaction between AXL and GAS6 and inhibits tumour cell migration and invasion induced by GAS6. Thus, DAXL-88 offers promise for the development of targeted therapeutic strategies in solid tumours, leukaemias and other lymphoid neoplasms.
journal_name
Scand J Immunoljournal_title
Scandinavian journal of immunologyauthors
Duan Y,Luo L,Qiao C,Li X,Wang J,Liu H,Zhou T,Shen B,Lv M,Feng Jdoi
10.1111/sji.12777subject
Has Abstractpub_date
2019-08-01 00:00:00pages
e12777issue
2eissn
0300-9475issn
1365-3083journal_volume
90pub_type
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journal_title：Scandinavian journal of immunology
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journal_title：Scandinavian journal of immunology
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journal_title：Scandinavian journal of immunology
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journal_title：Scandinavian journal of immunology
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pub_type： 杂志文章
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journal_title：Scandinavian journal of immunology
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journal_title：Scandinavian journal of immunology
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更新日期：2001-04-01 00:00:00
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journal_title：Scandinavian journal of immunology
pub_type： 杂志文章
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更新日期：1993-04-01 00:00:00
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journal_title：Scandinavian journal of immunology
pub_type： 杂志文章
doi：10.1111/j.1365-3083.1981.tb00191.x
更新日期：1981-08-01 00:00:00
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journal_title：Scandinavian journal of immunology
pub_type： 杂志文章,评审
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更新日期：2001-05-01 00:00:00
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journal_title：Scandinavian journal of immunology
pub_type： 历史文章,杂志文章,评审
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journal_title：Scandinavian journal of immunology
pub_type： 杂志文章
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journal_title：Scandinavian journal of immunology
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journal_title：Scandinavian journal of immunology
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doi：10.1111/j.1365-3083.1989.tb01190.x
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journal_title：Scandinavian journal of immunology
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更新日期：1976-01-01 00:00:00
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journal_title：Scandinavian journal of immunology
pub_type： 杂志文章
doi：10.1111/j.1365-3083.1993.tb02562.x
更新日期：1993-03-01 00:00:00
