Ianalumab (VAY-736) (FUT8-KO) is an anti- BAFF-R monoclonal antibody expressed in CHO cells with the fucosyltransferase 8 gene (FUT8) knocked out. Fucose depletion enhances its B cell clearance capacity. Ianalumab (FUT8-KO) competitively blocks the binding of BAFF to BAFF-R, inhibits the BAFF-mediated alternative NF-κB pro-survival signaling pathway, and abrogates the apoptotic ( apoptosis ) protective effect of BAFF on cancer cells. Ianalumab (FUT8-KO) can be used in research related to primary Sjögren's syndrome and chronic lymphocytic leukemia [1] [2].
In Vivo, Ianalumab (FUT8-KO) (100 mg/kg; Retro-orbital injection; once weekly; 2 weeks) reduces circulating chronic lymphocytic leukemia cell counts and percentages in Eμ-TCL1 transgenic mice, with effects sustained for at least 80 days[2]. Ianalumab (FUT8-KO) (10 mg/kg; Retro-orbital injection; once weekly; up to 6 weeks) improves survival and reduces chronic lymphocytic leukemia burden in SCID mice engrafted with leukemic Eμ-TCL1 splenocytes compared to ibrutinib monotherapy[2]. Combination treatment withIanalumab (FUT8-KO) (10 mg/kg; Retro-orbital injection; once weekly; up to 6 weeks) and ibrutinib significantly improves survival and reduces chronic lymphocytic leukemia burden in SCID mice engrafted with leukemic Eμ-TCL1 splenocytes compared to either monotherapy alone[2].
In Vitro, Ianalumab (FUT8-KO) (10 μg/mL) blocks the activation of the alternative NF-κB pathway in BAFF-mediated primary CLL B cells and primary CLL B cells treated with Ibrutinib by inhibiting p100 degradation and p52 nuclear translocation[2]. Ianalumab (FUT8-KO) (0.1-10 μg/mL) induces higher IFN-γ levels in primary CLL NK cells than Obinutuzumab at a concentration of 10 μg/mL[2]. Ianalumab (FUT8-KO) induces TNF-α production in primary monocytes and monocyte-derived macrophages from patients with chronic lymphocytic leukemia (CLL)[2]. Ianalumab (FUT8-KO) induces antibody-dependent cellular phagocytosis of primary chronic lymphocytic leukemia (CLL) B cells by monocyte-derived macrophages, at levels comparable to those of clinically relevant CD20-targeting antibodies[2].
References:
[1]. Dörner T, et al. Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Ann Rheum Dis. 2019;78(5):641-647.
[2]. McWilliams EM, et al. Anti-BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib. Blood Adv. 2019;3(3):447-460.
In Vivo, Ianalumab (FUT8-KO) (100 mg/kg; Retro-orbital injection; once weekly; 2 weeks) reduces circulating chronic lymphocytic leukemia cell counts and percentages in Eμ-TCL1 transgenic mice, with effects sustained for at least 80 days[2]. Ianalumab (FUT8-KO) (10 mg/kg; Retro-orbital injection; once weekly; up to 6 weeks) improves survival and reduces chronic lymphocytic leukemia burden in SCID mice engrafted with leukemic Eμ-TCL1 splenocytes compared to ibrutinib monotherapy[2]. Combination treatment withIanalumab (FUT8-KO) (10 mg/kg; Retro-orbital injection; once weekly; up to 6 weeks) and ibrutinib significantly improves survival and reduces chronic lymphocytic leukemia burden in SCID mice engrafted with leukemic Eμ-TCL1 splenocytes compared to either monotherapy alone[2].
In Vitro, Ianalumab (FUT8-KO) (10 μg/mL) blocks the activation of the alternative NF-κB pathway in BAFF-mediated primary CLL B cells and primary CLL B cells treated with Ibrutinib by inhibiting p100 degradation and p52 nuclear translocation[2]. Ianalumab (FUT8-KO) (0.1-10 μg/mL) induces higher IFN-γ levels in primary CLL NK cells than Obinutuzumab at a concentration of 10 μg/mL[2]. Ianalumab (FUT8-KO) induces TNF-α production in primary monocytes and monocyte-derived macrophages from patients with chronic lymphocytic leukemia (CLL)[2]. Ianalumab (FUT8-KO) induces antibody-dependent cellular phagocytosis of primary chronic lymphocytic leukemia (CLL) B cells by monocyte-derived macrophages, at levels comparable to those of clinically relevant CD20-targeting antibodies[2].
References:
[1]. Dörner T, et al. Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Ann Rheum Dis. 2019;78(5):641-647.
[2]. McWilliams EM, et al. Anti-BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib. Blood Adv. 2019;3(3):447-460.