Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a
protein that in humans is encoded by the TFRCgene.[5][6] TfR1 is required for iron import from
transferrin into cells by
endocytosis.[7][8]
Structure and function
TfR1 is a transmembrane glycoprotein composed of two disulfide-linked monomers joined by two disulfide bonds. Each monomer binds one holo-
transferrin molecule creating an iron-Tf-TfR complex which enters the cell by endocytosis.[9]
Clinical significance
TfR1 as a potential new target in cases of human leukemia & lymphoma. InatherYs, in Évry, France, developed a candidate drug, INA01 antibody (anti-CD71) that showed efficacy in pre-clinical studies in the therapy of two incurable orphan oncohematological diseases: the adult T cell leukemia (ATLL) caused by HTLV-1 and the Mantle cell lymphoma (MCL).[citation needed]
TfR1 expressed on the
endothelial cells of the
blood-brain barrier (BBB) is used also in
preclinical research to allow the delivery of large molecules including
antibodies into the
brain.[10] Some of the TfR1 targeting
antibodies have been shown to cross the
blood-brain barrier, without interfering with the uptake of iron. Amongst those are the mouse anti rat-TfR antibody OX26[11] and the rat anti mouse-TfR antibody 8D3.[12] The
affinity of the antibody-TfR interaction seems to be important determining the success of transcytotic transport over endothelial cells of the BBB. Monovalent TfR interaction favors BBB transport due to altered intracellular sorting pathways.
Avidity effects of bivalent interactions redirecting transport to the
lysosome.[13] Also, reducing TfR binding affinity directly promote dissociation from the TfR which increase brain parenchymal exposure of the TfR binding antibody.[14]
CD71 is a robust
immunohistochemistry marker for chorionic villi, especially in necrotic specimens. Among white blood cells and precursors, CD71 is expressed only by erythroid precursors within the normal hematopoietic marrow and spleen, in contrast to glycophorin that marks all types of red blood cells.[18]
^Pardridge WM, Buciak JL, Friden PM (October 1991). "Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo". The Journal of Pharmacology and Experimental Therapeutics. 259 (1): 66–70.
PMID1920136.
^Lee HJ, Engelhardt B, Lesley J, Bickel U, Pardridge WM (March 2000). "Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse". The Journal of Pharmacology and Experimental Therapeutics. 292 (3): 1048–52.
PMID10688622.
^Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, et al. (May 2011). "Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target". Science Translational Medicine. 3 (84): 84ra44.
doi:
10.1126/scitranslmed.3002230.
PMID21613623.
S2CID34161824.
1cx8: CRYTAL STRUCTURE OF THE ECTODOMAIN OF HUMAN TRANSFERRIN RECEPTOR
1de4: HEMOCHROMATOSIS PROTEIN HFE COMPLEXED WITH TRANSFERRIN RECEPTOR
1suv: Structure of Human Transferrin Receptor-Transferrin Complex
2nsu: Crystal structure of the ectodomain of human transferrin receptor fitted into a cryo-EM reconstruction of canine parvovirus and feline transferrin receptor complex