CD39 and CD73 as Promising Therapeutic Targets: What Could Be the Limitations?

Battastini, Ana Maria Oliveira; Figueiró, Fabrício; Leal, Daniela Bitencourt Rosa; Doleski, Pedro H.; Schetinger, Maria Rosa Chitolina

doi:10.3389/fphar.2021.633603

Cited by 27 publications

(28 citation statements)

References 54 publications

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“…To further improve the efficacy of tumor immunotherapy, many inhibitors of the CD39‐CD73‐A2AR pathway have been developed. [ 23 , 24 , 25 , 26 ] AZD4635 is an A2AR antagonist with high affinity and specificity for A2AR. AZD4635 as a single agent and in combination with durvalumab (anti‐PD‐L1 antibody) in patients with solid malignancies which is currently in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

Wang

et al. 2022

Advanced Science

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Due to the aggregation-caused quenching effect and near-infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging and photoactivated treatment are limited. Therefore, new near-infrared II (NIR-II) molecule (named TST), which had the abilities of aggregation-induced emission (AIE) and photothermal therapy are synthesized. Moreover, in order to further improve its fluorescent yield and therapeutic effect, camptothecin prodrug (CPT-S-PEG) and novel immune checkpoint inhibitor AZD4635 are used to co-assemble with TST into nanoparticles for drug delivery. On account of the strong interaction of camptothecin and TST, the intramolecular rotation of TST is limited, thereby inhibiting non-radiation attenuation and promoting fluorescence generation when the nanoparticles are intact. As nanoparticles uptake by cancer cells, redox sensitive CPT-S-PEG is degraded and the nanoparticles disintegrate. The released TST enhances non-radiative attenuation and expedites photothermal conversion because of the removal of the constraint of camptothecin. Furthermore, photothermal therapy induces immunogenic cell death of cancer cells and releases abundant ATP into the tumor microenvironment to recruit immune cells. However, superfluous ATP is converted into immunosuppressive adenosine through the CD39-CD73-A2AR pathway. The AZD4635 released by photothermal disintegration of the nanoparticles just blocks this pathway timely, achieving favorable synergistic effect of photothermal therapy, chemotherapy, and immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

Wang

et al. 2022

Advanced Science

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“…Cancer therapies are in development to specifically target CD39, and being analyzed in early clinical trials (ClinicalTrials.gov: NCT04306900, NCT03884556). The evidence is growing to also consider CD73 as a potential target [73]. For example, Briceño et al [74] recently published on the autocrine effect of CD73-mediated adenosine production, which limits the differentiation and metabolic fitness of CD8+ T cells.…”

Section: Adenosine (Ado) In the Tme: Potent Mediator Of Immunosuppressionmentioning

confidence: 99%

“…Even at this early stage in the field of liquid biopsy, the authors concluded that longitudinal blood sampling offered a way to monitor tumor genetic dynamics [96]. Fortunately, they were not alone in their success in the years that followed, other research groups also succeeded in detecting microvesicles such as GDEs in peripheral blood [71][72][73]. For instance, in 2018, Manda et al presented exosomes as biomarkers for detecting EGFR-positive high-grade gliomas [103].…”

Section: Exosomes In Diagnostics: Highly Promising Candidates For Liquid Biopsymentioning

confidence: 99%

Exosomes: Small EVs with Large Immunomodulatory Effect in Glioblastoma

Benecke

Coray

Umbricht

et al. 2021

IJMS

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Glioblastomas are among the most aggressive tumors, and with low survival rates. They are characterized by the ability to create a highly immunosuppressive tumor microenvironment. Exosomes, small extracellular vesicles (EVs), mediate intercellular communication in the tumor microenvironment by transporting various biomolecules (RNA, DNA, proteins, and lipids), therefore playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Exosomes are found in all body fluids and can cross the blood–brain barrier due to their nanoscale size. Recent studies have highlighted the multiple influences of tumor-derived exosomes on immune cells. Owing to their structural and functional properties, exosomes can be an important instrument for gaining a better molecular understanding of tumors. Furthermore, they qualify not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting aggressive tumor cells, like glioblastomas.

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“…However, inhibitors like suramin bind to P2 receptors and antagonize their effects ( Munkonda et al., 2007 ). Since these chemicals are not CD39-specific, their use has been shown to be limited ( Battastini et al., 2021 ). Other classes have been reported as inhibitors of E-NTPDases, such as polyoxometalates (POMs) ( Lee et al., 2015 ; Schachter et al., 2015 ; Jeffrey et al., 2020 ), thiadiazolopyrimidones ( Afzal et al., 2020 ), Schiff bases of tryptamine ( Kanwal et al., 2019 ), quinoline ( Hayat et al., 2019 ; Murtaza et al., 2021 ) and anthraquinone derivatives ( Al-Rashida and Iqbal, 2014 ; Baqi et al., 2020 ), sulfopolysaccharides ( Lopez et al., 2021 ) and carboxamide derivatives ( Afzal et al., 2021 ).…”

Section: Development Of E-ntpdases Inhibitorsmentioning

confidence: 99%

E-NTPDases: Possible Roles on Host-Parasite Interactions and Therapeutic Opportunities

Paes-Vieira

Gomes-Vieira

Meyer‐Fernandes

2021

Front. Cell. Infect. Microbiol.

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Belonging to the GDA1/CD39 protein superfamily, nucleoside triphosphate diphosphohydrolases (NTPDases) catalyze the hydrolysis of ATP and ADP to the monophosphate form (AMP) and inorganic phosphate (Pi). Several NTPDase isoforms have been described in different cells, from pathogenic organisms to animals and plants. Biochemical characterization of nucleotidases/NTPDases has revealed the existence of isoforms with different specificities regarding divalent cations (such as calcium and magnesium) and substrates. In mammals, NTPDases have been implicated in the regulation of thrombosis and inflammation. In parasites, such as Trichomonas vaginalis, Trypanosoma spp., Leishmania spp., Schistosoma spp. and Toxoplasma gondii, NTPDases were found on the surface of the cell, and important processes like growth, infectivity, and virulence seem to depend on their activity. For instance, experimental evidence has indicated that parasite NTPDases can regulate the levels of ATP and Adenosine (Ado) of the host cell, leading to the modulation of the host immune response. In this work, we provide a comprehensive review showing the involvement of the nucleotidases/NTPDases in parasites infectivity and virulence, and how inhibition of NTPDases contributes to parasite clearance and the development of new antiparasitic drugs.

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CD39 and CD73 as Promising Therapeutic Targets: What Could Be the Limitations?

Cited by 27 publications

References 54 publications

Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

Exosomes: Small EVs with Large Immunomodulatory Effect in Glioblastoma

E-NTPDases: Possible Roles on Host-Parasite Interactions and Therapeutic Opportunities

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