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Carbonic anhydrase 2-derived drug-responsive domain regulates membrane-bound cytokine expression and function in engineered T cells.
Commun Biol
January 2025
Obsidian Therapeutics, Cambridge, MA, USA.
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).
View Article and Find Full Text PDFSuperacid-Synthesized Fluorinated Diamines Act as Selective hCA IV Inhibitors.
J Med Chem
November 2024
Superacid Group in "Organic Synthesis" Team, Université de Poitiers, CNRS UMR 7285 IC2MP, Bât. B28, 4 rue Michel Brunet, TSA 51106, 86073 Poitiers Cedex 09, France.
Carbonic anhydrase (CA) IV is a membrane-bound enzyme involved in important physio-pathological processes, such as excitation-contraction coupling in heart muscle, central nervous system (CNS) extracellular buffering, and mediation of inflammatory response after stroke. Known since the mid-1980s, this isoform is still largely unexplored when compared to other isoforms, mostly for the current lack of inhibitors targeting selectively this isoform. The discovery of selective CA IV inhibitors is thus largely awaited.
View Article and Find Full Text PDFTrogocytosis is an underappreciated phenomenon that shapes the immune microenvironment surrounding many types of solid tumors. The consequences of membrane-bound proteins being deposited from a donor immune cell to a recipient cancer cell via trogocytosis are still unclear. Here, we report that human clear cell renal carcinoma tumors stably express the lymphoid markers CD45, CD56, CD14, and CD16.
View Article and Find Full Text PDFThe physiological significance of plasma-accessible carbonic anhydrase in the respiratory systems of fishes.
J Comp Physiol B
October 2024
Marine Science Institute, University of Texas at Austin, Port Aransas, TX, 78373, USA.
Carbonic anhydrase (CA) activity is ubiquitously found in all vertebrate species, tissues and cellular compartments. Most species have plasma-accessible CA (paCA) isoforms at the respiratory surfaces, where the enzyme catalyzes the conversion of plasma bicarbonate to carbon dioxide (CO) that can be excreted by diffusion. A notable exception are the teleost fishes that appear to lack paCA at their gills.
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