PMC:6562565 / 59973-61561 JSONTXT

{"project":"MyTest","denotations":[{"id":"31244820-24489992-35366351","span":{"begin":72,"end":75},"obj":"24489992"},{"id":"31244820-21638125-35366352","span":{"begin":95,"end":97},"obj":"21638125"},{"id":"31244820-24266925-35366353","span":{"begin":469,"end":472},"obj":"24266925"},{"id":"31244820-27622332-35366354","span":{"begin":705,"end":708},"obj":"27622332"},{"id":"31244820-27622332-35366355","span":{"begin":837,"end":840},"obj":"27622332"},{"id":"31244820-27622332-35366356","span":{"begin":984,"end":987},"obj":"27622332"},{"id":"31244820-27622332-35366357","span":{"begin":1194,"end":1197},"obj":"27622332"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Combinations of Adenosine-Axis Blockade Agents\nConcurrent mAb-mediated (418) or pharmacologic (47) inhibition of CD39 and CD73 failed to potentiate CD73-blockade-induced suppression of adenosine production by Tregs and ovarian cancer cell lines. These findings are corroborated by the observation that skin biopsies derived from CD39−/−CD73−/− mice have identical capacity to produce adenosine upon injury induction with counterpart biopsies derived from CD73−/− mice (424).\nAlone the same lines, others addressed whether simultaneous blockade of CD73 and of A2AR would result in higher anti-tumor efficacy. Of note, CD73−/−A2AR−/− mice present superior tumor control as compared to single knockout mice (384). Moreover, tumors in A2AR-null mice express twice as much CD73 at their core when compared to tumors formed in wild-type mice (384). Indeed, dual therapy with an anti-CD73 mAb and an A2AR agonist confers superior tumor protection as compared to either one as a monotherapy (384). However, this additive effect is lost when CD73 is targeted with a pharmacologic inhibitor, thus underscoring the capacity of CD73 to promote tumor progression in a catalytic activity-independent manner (384). In light of these studies, Evotec and Exscientia have partnered to develop A2AR/CD73 bi-specific inhibitory molecules (425), whereas NCT03454451, NCT03549000 as well as the Phase Ib/II clinical trial NCT03381274 sponsored by MedImmune all include solid tumor-bearing patient cohorts scheduled to be treated with combinations of an anti-CD73 mAb along with a pharmacologic A2AR antagonist."}

{"project":"TEST0","denotations":[{"id":"31244820-25-32-3850499","span":{"begin":72,"end":75},"obj":"[\"24489992\"]"},{"id":"31244820-48-54-3850500","span":{"begin":95,"end":97},"obj":"[\"21638125\"]"},{"id":"31244820-223-230-3850501","span":{"begin":469,"end":472},"obj":"[\"24266925\"]"},{"id":"31244820-97-104-3850502","span":{"begin":705,"end":708},"obj":"[\"27622332\"]"},{"id":"31244820-126-133-3850503","span":{"begin":837,"end":840},"obj":"[\"27622332\"]"},{"id":"31244820-141-148-3850504","span":{"begin":984,"end":987},"obj":"[\"27622332\"]"},{"id":"31244820-204-211-3850505","span":{"begin":1194,"end":1197},"obj":"[\"27622332\"]"}],"text":"Combinations of Adenosine-Axis Blockade Agents\nConcurrent mAb-mediated (418) or pharmacologic (47) inhibition of CD39 and CD73 failed to potentiate CD73-blockade-induced suppression of adenosine production by Tregs and ovarian cancer cell lines. These findings are corroborated by the observation that skin biopsies derived from CD39−/−CD73−/− mice have identical capacity to produce adenosine upon injury induction with counterpart biopsies derived from CD73−/− mice (424).\nAlone the same lines, others addressed whether simultaneous blockade of CD73 and of A2AR would result in higher anti-tumor efficacy. Of note, CD73−/−A2AR−/− mice present superior tumor control as compared to single knockout mice (384). Moreover, tumors in A2AR-null mice express twice as much CD73 at their core when compared to tumors formed in wild-type mice (384). Indeed, dual therapy with an anti-CD73 mAb and an A2AR agonist confers superior tumor protection as compared to either one as a monotherapy (384). However, this additive effect is lost when CD73 is targeted with a pharmacologic inhibitor, thus underscoring the capacity of CD73 to promote tumor progression in a catalytic activity-independent manner (384). In light of these studies, Evotec and Exscientia have partnered to develop A2AR/CD73 bi-specific inhibitory molecules (425), whereas NCT03454451, NCT03549000 as well as the Phase Ib/II clinical trial NCT03381274 sponsored by MedImmune all include solid tumor-bearing patient cohorts scheduled to be treated with combinations of an anti-CD73 mAb along with a pharmacologic A2AR antagonist."}

{"project":"2_test","denotations":[{"id":"31244820-24489992-35366351","span":{"begin":72,"end":75},"obj":"24489992"},{"id":"31244820-21638125-35366352","span":{"begin":95,"end":97},"obj":"21638125"},{"id":"31244820-24266925-35366353","span":{"begin":469,"end":472},"obj":"24266925"},{"id":"31244820-27622332-35366354","span":{"begin":705,"end":708},"obj":"27622332"},{"id":"31244820-27622332-35366355","span":{"begin":837,"end":840},"obj":"27622332"},{"id":"31244820-27622332-35366356","span":{"begin":984,"end":987},"obj":"27622332"},{"id":"31244820-27622332-35366357","span":{"begin":1194,"end":1197},"obj":"27622332"}],"text":"Combinations of Adenosine-Axis Blockade Agents\nConcurrent mAb-mediated (418) or pharmacologic (47) inhibition of CD39 and CD73 failed to potentiate CD73-blockade-induced suppression of adenosine production by Tregs and ovarian cancer cell lines. These findings are corroborated by the observation that skin biopsies derived from CD39−/−CD73−/− mice have identical capacity to produce adenosine upon injury induction with counterpart biopsies derived from CD73−/− mice (424).\nAlone the same lines, others addressed whether simultaneous blockade of CD73 and of A2AR would result in higher anti-tumor efficacy. Of note, CD73−/−A2AR−/− mice present superior tumor control as compared to single knockout mice (384). Moreover, tumors in A2AR-null mice express twice as much CD73 at their core when compared to tumors formed in wild-type mice (384). Indeed, dual therapy with an anti-CD73 mAb and an A2AR agonist confers superior tumor protection as compared to either one as a monotherapy (384). However, this additive effect is lost when CD73 is targeted with a pharmacologic inhibitor, thus underscoring the capacity of CD73 to promote tumor progression in a catalytic activity-independent manner (384). In light of these studies, Evotec and Exscientia have partnered to develop A2AR/CD73 bi-specific inhibitory molecules (425), whereas NCT03454451, NCT03549000 as well as the Phase Ib/II clinical trial NCT03381274 sponsored by MedImmune all include solid tumor-bearing patient cohorts scheduled to be treated with combinations of an anti-CD73 mAb along with a pharmacologic A2AR antagonist."}