Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.
Författare
Summary, in English
Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
Avdelning/ar
- Lymfom - Klinisk forskning
- Myelomgruppen
- Avdelningen för hematologi och transfusionsmedicin
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2015
Språk
Engelska
Sidor
473-488
Publikation/Tidskrift/Serie
Cancer Cell
Volym
27
Issue
4
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Lymphoma - Clinical Research
- Myeloma research group
ISBN/ISSN/Övrigt
- ISSN: 1878-3686