ARG2 Antibody
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Description
Introduction to ARG2 Antibody
ARG2 antibodies are therapeutic or research tools targeting Arginase 2 (ARG2), a mitochondrial enzyme that hydrolyzes L-arginine into ornithine and urea. ARG2 overexpression in cancers depletes extracellular arginine, suppressing T-cell proliferation and enabling immune evasion . Inhibitory ARG2 antibodies, such as C0021158, block this enzymatic activity, restoring antitumor immune responses . These antibodies are engineered to bind ARG2 with high specificity, avoiding cross-reactivity with its paralogue ARG1 .
Role of ARG2 in Disease and Therapeutic Targeting
ARG2 in Cancer Immunosuppression
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Overexpressed in pancreatic, colorectal, and acute myeloid leukemia (AML), ARG2 creates an arginine-depleted tumor microenvironment .
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Reduced arginine levels impair T-cell CD3ζ expression and proliferation, enabling tumor immune evasion .
Therapeutic Mechanism
ARG2 antibodies inhibit enzymatic activity via two strategies:
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Competitive inhibition: Directly blocking the substrate-binding site.
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Allosteric modulation: Inducing conformational changes at the active site (e.g., C0021158) .
Key Advances in Antibody Engineering
In Vitro Efficacy
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T-Cell Proliferation: 15 µg/mL ARG2 fully suppressed T-cells; C0021158 restored proliferation at 157 nM .
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Specificity: No cross-reactivity with ARG1 confirmed via bio-layer interferometry .
In Vivo Synergy
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Tumor Models: Arg2-deficient CD8+ T cells combined with PD-1 blockade reduced tumor growth synergistically .
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Pharmacokinetics: Antibody half-life (>7 days in primates) supports sustained arginine restoration .
Therapeutic Applications
| Indication | Mechanism | Status |
|---|---|---|
| Solid Tumors | Reverse ARG2-mediated immunosuppression | Preclinical validation |
| AML | Counteract ARG2 secretion by leukemic blasts | In vitro proof-of-concept |
Development Pipeline
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C0021158: Partnering sought for Phase I trials in oncology and non-oncology indications .
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Challenges: Avoidance of off-target effects and optimization of delivery to immunosuppressive niches .
Comparative Analysis of ARG2 Antibodies
| Parameter | C0021158 | Traditional Inhibitors |
|---|---|---|
| Affinity | 173 pM | Low (µM range) |
| Specificity | ARG2-only | ARG1/ARG2 cross-reactive |
| Mode | Allosteric | Competitive |
| Clinical Potential | High (antibody durability) | Limited (small-molecule instability) |
Future Directions
Product Specs
Buffer
PBS with 0.02% Sodium Azide, 50% Glycerol, pH 7.3. Store at -20°C. Avoid freeze/thaw cycles.
Lead Time
Generally, we can ship the products within 1-3 business days after receiving your orders. Delivery time may vary depending on the purchasing method or location. Please consult your local distributors for specific delivery time estimates.
Synonyms
ARG2 antibody; ARGI2_HUMAN antibody; Arginase II mitochondrial antibody; Arginase type II antibody; Arginase-2 antibody; arginase-2, mitochondrial antibody; Kidney arginase antibody; Kidney type arginase antibody; Kidney-type arginase antibody; L arginine amidinohydrolase antibody; L arginine ureahydrolase antibody; mitochondrial antibody; Non hepatic arginase antibody; Non-hepatic arginase antibody; Nonhepatic arginase antibody; Type II arginase antibody
Target Names
ARG2
Uniprot No.
Target Background
Function
Arginase-2 (ARG2) plays a crucial role in regulating extra-urea cycle arginine metabolism and downregulating nitric oxide synthesis. In extrahepatic tissues, ARG2 controls the availability of L-arginine, a substrate for nitric oxide synthase (NOS). Arginine metabolism significantly influences innate and adaptive immune responses. ARG2 is implicated in the negative regulation of activated CD4(+) and CD8(+) T cell survival. It may suppress inflammation-related signaling in asthmatic airway epithelium. ARG2 might contribute to the immune evasion of Helicobacter pylori by restricting M1 macrophage activation and polyamine metabolism. In fetal dendritic cells, ARG2 potentially promotes immune suppression and T cell TNF-alpha production during gestation. ARG2 regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation, ultimately impacting NOS3/eNOS dysfunction. Independently of its enzymatic activity, ARG2 can inhibit endothelial autophagy by influencing mTORC2 signaling. ARG2 is also involved in vascular smooth muscle cell senescence and apoptosis, independent of its enzymatic activity. Considering the presence of NOS in the penile corpus cavernosum smooth muscle, clitoral corpus cavernosum, and vagina, ARG2 plays a role in both male and female sexual arousal.
Gene References Into Functions
- Expression profiling revealed downregulation of miR-1299 alongside upregulation of arginase-2 (ARG2) in hyperpigmented skin of melasma patients. PMID: 28627081
- ARG2 promotes tumorigenesis, and human cytomegalovirus (HCMV) may contribute to glioblastoma multiforme (GBM) pathogenesis by upregulating ARG2. PMID: 27363017
- Fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2. These findings reveal a previously unknown role of dendritic cells within the developing fetus, indicating their role in mediating homeostatic immune-suppressive responses during gestation. PMID: 28614294
- Schizophrenia patients exhibited increased arginase II protein expression in the frontal cortex compared to controls. PMID: 27529679
- Research findings provide strong evidence that human cytomegalovirus reduces the level of microRNA-613, an anti-onco-miRNA in glioblastoma, primarily by downregulating the expression of arginase-2. PMID: 28718378
- Overexpression of AMP-activated protein kinase (AMPK) induced arginase II protein expression and viable cell numbers in human pulmonary artery smooth muscle cells. PMID: 28213467
- Data demonstrates that transfection with Arginase II-small interfering RNA prevented hypoxia-induced cell proliferation. PMID: 27475813
- Circulating Arginase 2 concentrations are elevated in clinical erectile dysfunction (ED) and are associated with an increased risk for ED. PMID: 26537638
- Arginase 2 impairs endothelial autophagy independently of the L-arginine ureahydrolase activity through activation of RPS6KB1 and inhibition of PRKAA, implicated in atherogenesis. PMID: 25484082
- High arginase II expression correlates with poor survival for patients with neuroblastoma. Neuroblastoma suppresses T-cell proliferation via arginase II expression and activity. PMID: 26054597
- A high-fat diet enhanced arginase-II expression/activity and p38mapk activity, associated with eNOS-uncoupling as evidenced by decreased nitric oxide. PMID: 25034973
- Arg-II, p38, and S6K1 form a positive circuit that regulates endothelial senescence and cardiovascular aging. PMID: 25635535
- OxLDL triggers retrograde translocation of arginase2 in aortic endothelial cells via ROCK and mitochondrial processing peptidase. PMID: 24903103
- These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells. PMID: 24860943
- It is speculated that cytomegalovirus may contribute to endothelial dysfunction via ARG II induction and reduced eNOS production. PMID: 24442486
- A study identified arginase II as a new target of miR-17-5p in human pulmonary artery smooth muscle cells (hPASMC), with miR-17-5p involved in the hypoxic induction of arginase II in hPASMC. Evidence supports a feedback loop between arginase II and miR-17-5p, where arginase II regulates miR-17-5p expression in hPASMC. PMID: 24879052
- Data indicate that arginase II (Arg II) expressions were higher in breast tumor tissues compared to the matched normal tissues. PMID: 24223914
- HDAC2 is a critical regulator of Arg2 expression, thereby influencing endothelial nitric oxide and endothelial function. PMID: 24833798
- Arg-II promotes mitochondrial dysfunction, leading to VSMC senescence/apoptosis through complex positive crosstalk among S6K1-JNK, ERK, p66Shc, and p53, contributing to an atherosclerotic vulnerability phenotype. PMID: 23832324
- Maternal hypercholesterolemia during pregnancy alters umbilical vein reactivity due to fetal endothelial dysfunction associated with arginase and eNOS signaling imbalance. PMID: 23950140
- Gene expression studies have identified altered expression of arginase 2 in suicide completers with a history of mood disorders. PMID: 23260169
- The presence of ARG2-expressing CAFs is an indicator of poor prognosis, as well as hypoxia, in pancreatic ductal carcinoma. PMID: 23424623
- Endothelial eNOS/arginase imbalance contributes to vascular dysfunction in IUGR umbilical and placental vessels. PMID: 23122700
- Arginase-II (ARG2) was expressed by 60 percent of head and neck squamous cell carcinomas. The absence of ARG2 expression was significantly associated with prolonged overall survival. PMID: 22815199
- The inhibition of arginase II protein was found to be mediated by exchange protein directly activated by cAMP. PMID: 22447968
- This study demonstrated that H3K4me3 modification plays a significant role in the upregulation of ARG2 in the prefrontal cortex. PMID: 22008221
- Data suggest that exposure to particulate matter (i.e., air pollutants) upregulates arginase II (but not arginase I) activity and expression in bronchial epithelial cells, in part, via epidermal growth factor-dependent signaling. PMID: 22712848
- DDIT3, STT3A, ARG2, and FAM129A immunohistochemistry do not appear to be useful in the diagnosis of thyroid follicular neoplasias, as they do not reliably distinguish follicular thyroid carcinoma from follicular thyroid adenoma. PMID: 22157935
- ARG2 plays a vascular role in placental vessels, counteracting NOS-dependent relaxation. PMID: 22391327
- Sequence variations in the NOS2A and ARG2 loci were globally associated with exhaled nitric oxide. PMID: 21039601
- This research delineates a clearer pathway from OxLDL through the endothelial cell LOX-1 receptor, RhoA, and ROCK, to the activation of arginase II, downregulation of NO, and vascular dysfunction in atherosclerosis. PMID: 21130456
- Gene silencing promotes apoptosis and reduces the expression of cell proliferation markers in thyroid cancer cells. PMID: 20542107
- In human lung microvascular endothelial cells, hypoxia upregulates arginase activity, as well as mRNA and protein levels of arginase II. Inhibition of arginase II by small interfering RNA or by the inhibitor BEC enhanced NO levels. PMID: 20861464
- The alteration of arginase activity between colostrum and mature milk may be a consequence of the transfer of arginase from the blood of the breast mother's mammary glands into the colostrum and mature milk. PMID: 20853600
- Arginase contributes significantly to L-proline supply for collagen synthesis in rat fibroblasts, in which arginase I is the predominant isoenzyme, but not in human fibroblasts, in which arginase II is the only isoenzyme expressed. PMID: 20107769
- Association of ARG2 gene polymorphism is present in adult asthma, exhibiting lower reversibility specifically with beta2 agonists. It is also associated with asthma severity, severe airway hyperresponsiveness, and less long-term response to inhaled corticosteroids. PMID: 20124949
- There was an overexpression of arginase II in anorexia nervosa patients. PMID: 20071203
- [Review] Arginase is constitutively expressed in endothelial cells, but expression of the specific isoforms differs among mammalian species. While some arginase I has been detected in human endothelial cells, the predominant isoform is arginase II. PMID: 19508396
- ARG2 plays a physiological role in male and female sexual arousal. PMID: 12859189
- Increased arginase II expression and activity are observed in pulmonary arterial hypertension. PMID: 15364894
- The ArgII gene is an early IRF-3-regulated gene that participates in the interferon-independent antiviral response through polyamine production and induction of apoptosis. PMID: 15955070
- The Asn149-->Asp mutation is proposed to generate a conformational change responsible for the altered substrate specificity of arginase II. PMID: 16128822
- Increasing L-Arg for NO synthesis, either through arginase inhibition or direct L-Arg supplementation, restores the age-related deficit in reflex cutaneous vasodilatation. PMID: 16675494
- ARG2 is observed in both cytotrophoblasts and syncytiotrophoblasts. PMID: 16720041
- Increased arginase II expression & activity suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease. PMID: 17353439
- Arginase II expression may play a role in prostate cancer progression. PMID: 18202758
- Cocoa flavonols lower ARG2 activity in endothelial cells in vitro and erythrocytes in vivo. PMID: 18348861
- ARG2 is expressed in lung cancer, but it does not induce tumor immune escape and does not affect disease progression, most likely due to the lack of concomitant NOS expression. PMID: 18528866
- siRNA silencing of arginase-II did not inhibit the up-regulation of endothelial VCAM-1, ICAM-1, and E-selectin by TNFalpha. PMID: 19284655
Database Links
Protein Families
Arginase family
Subcellular Location
Mitochondrion.
Tissue Specificity
Expressed most strongly in kidney and prostate, much less strongly in the brain, skeletal muscle, placenta, lung, mammary gland, macrophage, uterus, testis and gut, but apparently not in the liver, heart and pancreas. Expressed in activated T cells.
Customer Reviews
,
B.A
By Anonymous
★★★★★
Applications : WB
Sample type: Human HT-29 cell
Sample dilution: 1:1000
Review: Western-blot analysis showed that at 200 µM, compounds #1, #2, #4 and #5 upregulated arginase-2 protein expression as compared to untreated GT-29 cell.
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