Monoclonal antibodies raised against 167–180 aa sequence of human carbonic anhydrase XII inhibit its enzymatic activity

Dekaminaviciute, Dovile; Kairys, Visvaldas; Zilnyte, Milda; Petrikaitė, Vilma; Jogaite, Vaida; Matulienė, Jurgita; Gudlevičienė, Živilė; Vullo, Daniela; Supuran, Claudiu T.; Žvirblienė, Aurelija

doi:10.3109/14756366.2013.856424

Cited by 15 publications

(16 citation statements)

References 46 publications

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“…Although there are no clinical trials that specifically target CA XII to date, a patent was recently filed for 6A10 monoclonal antibody which specifically targets CA XII [ 3 , 103 , 104 ]. Studies have shown that 6A10 has an inhibitory effect on the CA activity of breast cancer cells overexpressing CA XII [ 105 ].…”

Section: Isoform Specific Targeting Of Cas In Cancermentioning

confidence: 99%

Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

et al. 2018

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Carbonic anhydrases (CAs) catalyze the reversible hydration of carbon dioxide to produce bicarbonate and a proton. Multiple CA isoforms are implicated in a range of diseases, including cancer. In solid tumors, continuously dividing cells create hypoxic conditions that eventually lead to an acidic microenvironment. Hypoxic tumor cells have different mechanisms in place to regulate and adjust the surrounding microenvironment for survival. These mechanisms include expression of CA isoform IX (CA IX) and XII (CA XII). These enzymes help maintain a physiological intracellular pH while simultaneously contributing to an acidic extracellular pH, leading to tumor cell survival. Expression of CA IX and CA XII has also been shown to promote tumor cell invasion and metastasis. This review discusses the characteristics of CA IX and CA XII, their mechanism of action, and validates their prospective use as anticancer targets. We discuss the current status of small inhibitors that target these isoforms, both classical and non-classical, and their future design in order to obtain isoform-specificity for CA IX and CA XII. Biologics, such as monoclonal antibodies, monoclonal-radionuclide conjugated chimeric antibodies, and antibody-small molecule conjugates are also discussed.

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Section: Isoform Specific Targeting Of Cas In Cancermentioning

confidence: 99%

Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

et al. 2018

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“…So far, little success has been made in identifying carbonic anhydrase-binding antibodies that also block CA enzymatic activity. 6A10 was the first and remains the best-described antibody for the inhibition of CA12 hydratase enzyme activity, with a potential biological role in the reduction of tumor growth 15,20,21 . However, only very few antibodies that can specifically bind and inhibit the hydratase activity of CA9 have appeared in the literature, such as the recently described MSC8 antibody 22,23 .…”

Section: Introductionmentioning

confidence: 99%

Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity

Uda

Seibert

Stenner

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) were proposed as potential targets for cancer therapy more than 20 years ago. However, to date, there are only very few antibodies that have been described to specifically target CA9 and CA12 and also block the enzymatic activity of their targets. One of the early stage bottlenecks in identifying CA9-and CA12-inhibiting antibodies has been the lack of a high-throughput screening system that would allow for rapid assessment of inhibition of the targeted carbon dioxide hydratase activity of carbonic anhydrases. In this study, we show that measuring the esterase activity of carbonic anhydrase offers a robust and inexpensive screening method for identifying antibody candidates that block both hydratase and esterase activities of carbonic anhydrase's. To our knowledge, this is the first implementation of a facile surrogate-screening assay to identify potential therapeutic antibodies that block the clinically relevant hydratase activity of carbonic anhydrases.

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“…Since these various compounds have been subject of numerous recent reviews, here we concentrate only on aromatic sulfonamides as CA inhibitors. Supuran’s group also measured the affinity of monoclonal antibodies to target CA isoforms using SFA ( Dekaminavičiūtė et al, 2014 ). In addition to other previously synthesized compounds containing fluorine, our group has identified a series of fluorinated benzenesulfonamides as strong CA IX inhibitors by SFA and have shown a correlation between parameters obtained by enzymatic and biophysical assays ( Dudutienė et al, 2014 ).…”

Section: Ca Inhibitor Assaysmentioning

confidence: 99%

An update on anticancer drug development and delivery targeting carbonic anhydrase IX

Kazokaitė

Aspatwar

Parkkila

et al. 2017

PeerJ

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The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors.

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Monoclonal antibodies raised against 167–180 aa sequence of human carbonic anhydrase XII inhibit its enzymatic activity

Cited by 15 publications

References 46 publications

Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity

An update on anticancer drug development and delivery targeting carbonic anhydrase IX

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