dc.contributor.authorTay, Hui Min
dc.date.accessioned2019-05-08T13:17:21Z
dc.date.available2019-05-08T13:17:21Z
dc.date.issued2019
dc.identifier.urihttp://hdl.handle.net/10356/77108
dc.description.abstractAdenosine is an anti-inflammatory and immunosuppressive metabolite that binds to the adenosine receptors (AR) - A1R, A2AR, A2BR and A3R. Adenosine immunosuppression is mediated via A2Rs, with A2BR only activated by high adenosine concentration such as within solid tumor microenvironments (TME). A2BR has been shown to be predominantly overexpressed and correlated to poor prognosis in several cancers, hence inhibiting A2BR can specifically enhance anti-tumor immune response. In this study, 5 A2BR inhibitors (A2BRi) were screened against a clinically approved A2ARi. Functional readout assays were identified to show that cell viability and proliferation of T and NK cells were rescued by A2BRi. Adenosine at 0.1mM was concluded appropriate to study these effects in healthy peripheral-blood mononuclear cells (PBMCs). Furthermore, to mimic pathophysiological adenosine production, a TME model was developed and uncovered a previously undetectable A2BRi T-cell proliferation response. An innovative adenosine production assay developed confirmed the greater adenosine - 4-fold in tumor than normal tissue. A screening workflow was thereupon established. With only one current A2BRi clinical trial, we close the gap and collectively detected novel A2BRi with promising computational medicinal chemistry data and dose-dependent immunomodulation. ISAM-140 and Cmpd5 comparably improved T and NK cell proliferation with potential superiority than A2ARi.en_US
dc.format.extent33 p.en_US
dc.language.isoenen_US
dc.rightsNanyang Technological University
dc.subjectDRNTU::Science::Biological sciencesen_US
dc.titleTargeting adenosine-2 B receptor : a potential metabolic immune checkpointen_US
dc.typeFinal Year Project (FYP)en_US
dc.contributor.supervisorAndreas Lundqvisten_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.degreeBachelor of Science in Biological Sciencesen_US
dc.contributor.organizationKarolinska Instituteen_US


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