دورية أكاديمية
أعرض في EDS

Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors.

التفاصيل البيبلوغرافية
العنوان: Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors.
المؤلفون: Wang L; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Londono LM; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Cowell J; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Saatci O; Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, South Carolina., Aras M; Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, South Carolina., Ersan PG; Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, South Carolina., Serra S; Department of Medical Sciences, University of Torino, Turin, Italy., Pei H; La Jolla Institute for Immunology, La Jolla, California., Clift R; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Zhao Q; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Phan KB; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Huang L; Formerly of Halozyme Therapeutics, Inc., San Diego, California., LaBarre MJ; Halozyme Therapeutics, Inc., San Diego, California., Li X; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Shepard HM; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Deaglio S; Department of Medical Sciences, University of Torino, Turin, Italy., Linden J; La Jolla Institute for Immunology, La Jolla, California., Thanos CD; Formerly of Halozyme Therapeutics, Inc., San Diego, California., Sahin O; Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, South Carolina., Cekic C; Formerly of Halozyme Therapeutics, Inc., San Diego, California. caglarcekic@gmail.com.
المصدر: Cancer research [Cancer Res] 2021 Jun 15; Vol. 81 (12), pp. 3319-3332. Date of Electronic Publication: 2021 Apr 16.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, Md. : American Association for Cancer Research
Original Publication: Chicago [etc.]
مواضيع طبية MeSH: Adenosine/*antagonists & inhibitors , Adenosine Deaminase/*metabolism , Intercellular Signaling Peptides and Proteins/*metabolism , Neoplasms/*prevention & control, Adenosine Deaminase/genetics ; Animals ; Apoptosis ; Cell Proliferation ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Neoplasms/enzymology ; Neoplasms/pathology ; Prognosis ; Survival Rate ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
مستخلص: Extracellular adenosine in tumors can suppress immune responses and promote tumor growth. Adenosine deaminase 2 (ADA2) converts adenosine into inosine. The role of ADA2 in cancer and whether it can target adenosine for cancer therapy has not been investigated. Here we show that increased ADA2 expression is associated with increased patient survival and enrichment of adaptive immune response pathways in several solid tumor types. Several ADA2 variants were created to improve catalytic efficiency, and PEGylation was used to prolong systemic exposure. In mice, PEGylated ADA2 (PEGADA2) inhibited tumor growth by targeting adenosine in an enzyme activity-dependent manner and thereby modulating immune responses. These findings introduce endogenous ADA2 expression as a prognostic factor and PEGADA2 as a novel immunotherapy for cancer. SIGNIFICANCE: This study identifies ADA2 as a prognostic factor associated with prolonged cancer patient survival and introduces the potential of enzymatic removal of adenosine with engineered ADA2 for cancer immunotherapy.
(©2021 American Association for Cancer Research.)
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المشرفين على المادة: 0 (Intercellular Signaling Peptides and Proteins)
EC 3.5.4.4 (ADA2 protein, human)
EC 3.5.4.4 (Adenosine Deaminase)
K72T3FS567 (Adenosine)
تواريخ الأحداث: Date Created: 20210417 Date Completed: 20211214 Latest Revision: 20211214
رمز التحديث: 20240628
DOI: 10.1158/0008-5472.CAN-21-0340
PMID: 33863778
قاعدة البيانات: MEDLINE
الوصف
تدمد:1538-7445
DOI:10.1158/0008-5472.CAN-21-0340