Free L-Arginine
(Arg) is provided by the diet, de novo synthesis, and
protein turnover. De novo synthesis is important enough not to consider Arg as an
essential amino acid. However, in some circumstances - e.g. early development,
infection, and inflammation - de novo synthesis is not sufficient and requires
dietary Arg, which is thus classified as a conditionally-essential amino acid.
Whatever the source, Arg can be
metabolized through different degrading pathways which include i) the nitric
oxide synthase (NOS) pathway providing
Citrulline and NO, as well as ii) the well-known Arginase pathway leading to
the production of Urea and L-Ornithine (Orn).
In mammals, through a limited
amount of Arg and the concomitant production of Orn, elevated
Arginase activity has been linked to dysfunctions and pathologies of the
cardiovascular system, kidneys, and central nervous system, as well as to
dysfunction of the immune system and cancer (1). In the
context of oncology, Arginase - types 1 & 2 - can be expressed by tumor
cells or immune cell subsets including Myeloid Derived Suppressive Cells
(MDSCs), and, through its metabolic activity, creates an immunosuppressive
milieu. As to restore an effective anti-tumor immune response, blocking the Arginase
pathway has been considered an attractive immunotherapeutic strategy (2).
Given the importance of this
metabolic pathway in pathophysiological processes and in particular in immune
regulation, we have developed and validated a robust and easy-to-use
immunoassay (#ISE-0410R) for the
simultaneous detection and quantification of both Arg and Orn in plasma /
serum from multiple species.
Using a
syngeneic MC38 mouse colorectal tumor model, we evaluated, using our immunoassay, Arg and
Orn serum levels upon animal treatment with a single or five consecutive
injections of the prototypical Arginase inhibitor - INCB-1158 - or its respective
vehicle solution. This assay revealed the ability of INCB-1158 to restore the
level of Arg and limit, at the same time, Orn production. This dataset
confirms the robustness of our ELISA kits to quantify Orn and Arg levels as
well as the accuracy of Orn to Arg ratio as a surrogate of Arginase activity.
The arginase inhibitor INCB-1158
restores Arg level while limiting Orn production in sera of MC38-tumor bearing
mouse model. C57BL/6J mice were subcutaneously
inoculated with MC38 colorectal cancer cell line and treated orally with
100mg/kg of INCB-1158 for one or five consecutive days. Sera were collected
after each treatment period and subjected to Arg and Orn level quantification
using #IS-I-0400R and #IS-I-1000R ELISA
kits, respectively. Orn to Arg ratio was then calculated as a surrogate of Arginase
activity
PRODUCTS
#IS-I-0400R
#IS-I-1000R
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