MilliporeSigma
  • Home
  • Search Results
  • Effector-mediated eradication of precursor B acute lymphoblastic leukemia with a novel Fc-engineered monoclonal antibody targeting the BAFF-R.

Effector-mediated eradication of precursor B acute lymphoblastic leukemia with a novel Fc-engineered monoclonal antibody targeting the BAFF-R.

Molecular cancer therapeutics (2014-05-16)
Reshmi Parameswaran, Min Lim, Fei Fei, Hisham Abdel-Azim, Anna Arutyunyan, Isabelle Schiffer, Margaret E McLaughlin, Hermann Gram, Heather Huet, John Groffen, Nora Heisterkamp
ABSTRACT

B-cell activating factor receptor (BAFF-R) is expressed on precursor B acute lymphoblastic leukemia (pre-B ALL) cells, but not on their pre-B normal counterparts. Thus, selective killing of ALL cells is possible by targeting this receptor. Here, we have further examined therapeutic targeting of pre-B ALL based on the presence of the BAFF-R. Mouse pre-B ALL cells lacking BAFF-R function had comparable viability and proliferation to wild-type cells, but were more sensitive to drug treatment in vitro. Viability of human pre-B ALL cells was further reduced when antibodies to the BAFF-R were combined with other drugs, even in the presence of stromal protection. This indicates that inhibition of BAFF-R function reduces fitness of stressed pre-B ALL cells. We tested a novel humanized anti-BAFF-R monoclonal antibody optimalized for FcRγIII-mediated, antibody-dependent cell killing by effector cells. Antibody binding to human ALL cells was inhibitable, in a dose-dependent manner, by recombinant human BAFF. There was no evidence for internalization of the antibodies. The antibodies significantly stimulated natural killer cell-mediated killing of different human patient-derived ALL cells. Moreover, incubation of such ALL cells with these antibodies stimulated phagocytosis by macrophages. When this was tested in an immunodeficient transplant model, mice that were treated with the antibody had a significantly decreased leukemia burden in bone marrow and spleen. In view of the restricted expression of the BAFF-R on normal cells and the multiple anti-pre-B ALL activities stimulated by this antibody, a further examination of its use for treatment of pre-B ALL is warranted.

MATERIALS
Product Number
Brand
Product Description

Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
SAFC
L-Glutamine
Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, ≥90% (HPLC)
Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, BioReagent, suitable for fluorescence, mixture of 2 components, ≥90% (HPLC)
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Supelco
L-Glutamine, certified reference material, TraceCERT®
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, suitable for protein labeling, ≥90% (HPLC), powder
Sigma-Aldrich
Anti-BAFF antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
Sigma-Aldrich
Monoclonal Anti-TNFSF13B antibody produced in mouse, clone 1C11, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
BAFF active human, Animal-component free, recombinant, expressed in Nicotiana, >97% (SDS-PAGE)
Sigma-Aldrich
BAFF human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC)
Sigma-Aldrich
Anti-TNFSF13B antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-TNFSF13B antibody produced in mouse, clone 2C11, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-TNFSF13B antibody produced in mouse, clone 3G6, purified immunoglobulin, buffered aqueous solution