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Use of an anti-CD200 blocking antibody improves immune responses to AML in vitro and in vivo

Rastogi, N., Baker, S., Man, S., Uger, R., Wong, M., Coles, Steven ORCID: https://orcid.org/0000-0002-1109-6971, Hodges, M., Gilkes, A., Knapper, S., Darley, R. and Tonks, A. (2020) Use of an anti-CD200 blocking antibody improves immune responses to AML in vitro and in vivo. British Journal of Haematology. ISSN 1365-2141 (In Press)

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Abstract

Acute myeloid leukaemia (AML) is a highly heterogeneous disease in which leukaemic stem cell (LSC) persistence is considered to be the primary cause of relapse (Ivey et al, 2016). Immune evasion by LSC is an important determinant of relapse which is mediated by expression of specific cell surface molecules with immune modulatory function (Austin et al, 2016). Novel immune-directed therapeutic approaches form a major focus of current and clinical research (Hobo et al, 2018). We have previously shown that CD200 is an important immune checkpoint protein that is expressed in ~40% of AML patients and associates with poor prognosis (Tonks et al, 2007). CD200 belongs to the immunoglobulin superfamily and exerts immunosuppressive signaling through its receptor CD200R present on immune cells (Barclay et al, 2002). We have previously shown that CD200 High AML patients exhibited reduced Natural Killer (NK) and T-cell immune responses in comparison to CD200 Low patients, indicating that CD200 is a potential immunotherapeutic target in this disease. Our results also suggested that CD200 can be a contributing factor responsible for AML immune evasion and therapy relapse (Coles et al, 2011;Coles et al, 2012a;Coles et al, 2012b;Coles et al, 2015). With this in mind, we used an anti-CD200 blocking antibody (TTI-CD200) to assess whether CD200 mediated immunosuppression can be reversed in AML. TTI-CD200 is a fully human antibody that binds high affinity to human CD200 with a KD of 1.89 nM as determined through BIAcore analysis.

Item Type: Article
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Uncontrolled Discrete Keywords: AML, immunotherapy, leukaemia, leukaemia markers, therapy
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Divisions: College of Health, Life and Environmental Sciences > School of Science and the Environment
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Depositing User: Steven Coles
Date Deposited: 08 Sep 2020 09:48
Last Modified: 08 Sep 2020 09:48
URI: https://eprints.worc.ac.uk/id/eprint/9670

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