Abstract
APRIL (a proliferation-inducing ligand or TALL-2 and TRDL-1) is a member of the tumour necrosis factor (TNF) superfamily and binds two TNF receptors: TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B-cell maturation antigen). APRIL is important for the maintenance of humoral immune responses, although was originally discovered due to its role in promoting tumourigenic responses. APRIL has since been shown to be involved in several autoimmune diseases and is also implicated as an important pro-survival factor in several B-cell malignancies. To target APRIL specifically for therapeutic purposes, we are developing novel APRIL antagonistic monoclonal antibodies. Here we describe the characterisation of these antibodies and the future direction of our studies. In addition we have performed experiments to further decipher the role of heparan sulphate proteoglycan (HSPG) interactions in APRIL signalling. We report that the HSPG interaction provides a platform for APRIL cross-linking and oligomerisation to signal effectively via BCMA and TACI, but does not appear to mediate direct signalling. The role of APRIL in solid tumours lacking the known APRIL receptors is also addressed.
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