ArticleMolecular cancer therapeutics2014
Effector-mediated eradication of precursor B acute lymphoblastic leukemia with a novel Fc-engineered monoclonal antibody targeting the BAFF-R.
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Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
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- Molecular mechanisms of unique therapeutic potential of CUDC-907 for MEF2D fusion-driven BCP-ALL.Signal transduction and targeted therapy · 2025Article
- Opportunities and limitations of B cell depletion approaches in SLE.Nature reviews. Rheumatology · 2025Review
- Targeting chronic lymphocytic leukemia with B-cell activating factor receptor CAR T cells.MedComm · 2024Article
- Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies.Cancer immunology, immunotherapy : CII · 2023Article
- Generation of a humanized afucosylated BAFF-R antibody with broad activity against human B-cell malignancies.Blood advances · 2023Article
- Advancing Biologic Therapy for Refractory Autoimmune Hepatitis.Digestive diseases and sciences · 2022Review
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- CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia.Leukemia · 2022Article
- A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers.Nature communications · 2022Article
- CAR-T cell therapy for hematological malignancies: Limitations and optimization strategies.Frontiers in immunology · 2022Review
- The BAFF/NFκB axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.Cancer science · 2021Article
- TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss.Cancer cell international · 2021Article
- BAFF receptor antibody for mantle cell lymphoma therapy.Oncoimmunology · 2021Article
- Understanding the Immune-Stroma Microenvironment in B Cell Malignancies for Effective Immunotherapy.Frontiers in oncology · 2021Review
- Phage Display Derived Monoclonal Antibodies: From Bench to Bedside.Frontiers in immunology · 2020Review
- The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma.Frontiers in oncology · 2020Article
- CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies.Science translational medicine · 2019Article
- Combination Therapy for Treating Advanced Drug-Resistant Acute Lymphoblastic Leukemia.Cancer immunology research · 2019Article
- Anti-BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib.Blood advances · 2019Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Reshmi ParameswaranAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Min LimAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Fei FeiAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Hisham Abdel-AzimAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Anna ArutyunyanAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Isabelle SchifferAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Margaret E McLaughlinAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Hermann GramAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Heather HuetAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
John GroffenAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland.
Nora HeisterkampAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, SwitzerlandAuthors' Affiliations: Section of Molecular Carcinogenesis; Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute, Children's Hospital Los Angeles; Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Oncology Translational Medicine and Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Cambridge, Massachusetts; and Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel, Switzerland heisterk@hsc.usc.edu.
Novartis (United States) · USUniversity of Southern California · USNovartis Institutes for BioMedical ResearchNovartis (Switzerland) · CH
Funding
TREATMENT OF BCR/ABL CAUSED LEUKEMIAS WITH FTIsR01CA090321 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI HEISTERKAMP, NORA C · 2001 to 2017
$4.4MMicroenvironment-Leukemia Communication Through LectinsR01CA172040 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI HEISTERKAMP, NORA C · 2013 to 2017
$1.7MNCI NIH HHS CA090321NCI NIH HHS CA172040NCI NIH HHS R01 CA090321NCI NIH HHS R01 CA172040
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.
Indexed as
ImmunotherapyAnimalsAntibodies, Monoclonal, HumanizedB-Cell Activation Factor ReceptorCell Line, TumorHumansImmunoglobulin Fc FragmentsMiceMolecular Targeted TherapyPrecursor B-Cell Lymphoblastic Leukemia-LymphomaAntibodies, Monoclonal, HumanizedB-Cell Activation Factor ReceptorImmunoglobulin Fc FragmentsTNFRSF13C protein, human
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