Yazarlar : Guadagnoli M, Kimberley F, Phan U, Cameron K, Vink P, Rodermond H, Eldering E, Kater A, van Eenennaam H, Medema JP.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/21543761

Konu : Lösemi

Literatür İçeriği : APRIL (A proliferation inducing ligand) is a TNF family member that binds two TNF receptor family members, TACI and BCMA. It shares these receptors with the closely related TNF family member, B cell activating factor (BAFF). Contrary to BAFF, APRIL binds heparan sulphate proteoglycans (HSPGs), which regulates cross-linking of APRIL and efficient signaling. APRIL was originally identified as a growth promoter of solid tumors, and more recent evidence defines APRIL also as an important survival factor in several human B cell malignancies, such as Chronic Lymphocytic Leukemia (CLL). In order to target APRIL therapeutically, we developed two anti-human APRIL antibodies (hAPRIL.01A and hAPRIL.03A) that block APRIL binding to BCMA and TACI. Their antagonistic properties are unique when compared to a series of commercially available monoclonal anti-human APRIL antibodies as they prevent in vitro proliferation and IgA production of APRIL-reactive B cells. In addition, they effectively impair the CLL-like phenotype of aging APRIL transgenic mice and, more importantly, block APRIL binding to human B cell lymphomas and prevent the survival effect induced by APRIL. We therefore conclude that these antibodies have potential for further development as therapeutics to target APRIL-dependent survival in B cell malignancies.

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