Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity
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Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity. / Menzel, Stephan; Schwarz, Nicole; Haag, Friedrich; Koch-Nolte, Friedrich.
in: FRONT PHARMACOL, Jahrgang 9, 2018, S. 266.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity
AU - Menzel, Stephan
AU - Schwarz, Nicole
AU - Haag, Friedrich
AU - Koch-Nolte, Friedrich
PY - 2018
Y1 - 2018
N2 - Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+) are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies - single domain antibodies derived from heavy chain antibodies that naturally occur in camelids - display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.
AB - Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+) are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies - single domain antibodies derived from heavy chain antibodies that naturally occur in camelids - display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.
KW - Journal Article
KW - Review
U2 - 10.3389/fphar.2018.00266
DO - 10.3389/fphar.2018.00266
M3 - SCORING: Review article
C2 - 29636685
VL - 9
SP - 266
JO - FRONT PHARMACOL
JF - FRONT PHARMACOL
SN - 1663-9812
ER -