APRIL

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Ligands
APRIL (Human)

GtoPdb Ligand ID: 5068

Compound class: Endogenous peptide in human, mouse or rat

Comment: APRIL (also known as tumor necrosis factor ligand superfamily member 13; TNFSF13) is a protein of the TNF superfamily recognized by the cell surface catalytic receptor TACI [9] and other TNF family receptors [3]. Three APRIL isoforms have bee reported [1]. We provide the amino acid sequence for the mature peptide chain (i.e. without the 104 amino acid propeptide leader sequence which is cleaved by furin convertase in the Golgi apparatus prior to secretion [4]).

Species: Human

Immunopharmacology Comments
APRIL is essential for B cell development and long-term survival of plasma cells in the bone marrow [1]. APRIL and BAFF (B cell activating factor) are two B cell-stimulating molecules critical for maintenance of the B cell pool and humoral immunity. Biological function and evidence of involvement in the pathogenesis of a number of human autoimmune diseases has lead to investigation of the potential of tageting these molecules as novel drug targets [6]. Anti-APRIL mAbs are in clinical development, initially for the treatment of immunoglobulin A nephropathy (IgAN), which is an autoimmune disease that is characterised by the production of abnormally glycosylated and immune complex-forming IgA. Blocking APRIL binding to both the BCMA and TACI receptors is expected to ellicit disease-modifying effects in IgAN patients. Visterra's anti-APRIL mAb VIS649 is being advanced to Phase 2 clinical trial (NCT04287985), and Aduro Biotech began dosing IgAN patients with their mAb BION-1301 in June 2020 (NCT03945318).

Immunopharmacology Comments

APRIL is essential for B cell development and long-term survival of plasma cells in the bone marrow [1]. APRIL and BAFF (B cell activating factor) are two B cell-stimulating molecules critical for maintenance of the B cell pool and humoral immunity. Biological function and evidence of involvement in the pathogenesis of a number of human autoimmune diseases has lead to investigation of the potential of tageting these molecules as novel drug targets [6]. Anti-APRIL mAbs are in clinical development, initially for the treatment of immunoglobulin A nephropathy (IgAN), which is an autoimmune disease that is characterised by the production of abnormally glycosylated and immune complex-forming IgA. Blocking APRIL binding to both the BCMA and TACI receptors is expected to ellicit disease-modifying effects in IgAN patients. Visterra's anti-APRIL mAb VIS649 is being advanced to Phase 2 clinical trial (NCT04287985), and Aduro Biotech began dosing IgAN patients with their mAb BION-1301 in June 2020 (NCT03945318).

Immunopharmacology Disease
Disease	X-Refs	Comment	References
Systemic lupus erythematosus	Disease Ontology: DOID:9074 OMIM: 152700 Orphanet: ORPHA536	Investigational therapeutics targeting APRIL are under development- e.g. the fusion peptide atacicept for various autoinflammatory conditions, including SLE.	2