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Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.

Roghanian, Ali ; Teige, Ingrid LU ; Mårtensson, Linda LU ; Cox, Kerry L ; Kovacek, Mathilda LU ; Ljungars, Anne ; Mattson, Jenny LU ; Sundberg, Annika ; Vaughan, Andrew T and Shah, Vallari , et al. (2015) In Cancer Cell 27(4). p.473-488
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Cell
volume
27
issue
4
pages
473 - 488
publisher
Cell Press
external identifiers
  • pmid:25873171
  • wos:000352962600010
  • scopus:84928005736
  • pmid:25873171
ISSN
1878-3686
DOI
10.1016/j.ccell.2015.03.005
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Oncology, Kamprad Lab (013230901), Stem Cell Center (013041110), Division of Hematology and Transfusion Medicine (013041100), Tumour Biology, Malmö (013031300), Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019) Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:28.
id
23ee3f4d-5345-4d96-b34e-6c21ef067e22 (old id 5341867)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25873171?dopt=Abstract
date added to LUP
2016-04-01 10:58:32
date last changed
2022-04-28 03:14:13
@article{23ee3f4d-5345-4d96-b34e-6c21ef067e22,
  abstract     = {{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.}},
  author       = {{Roghanian, Ali and Teige, Ingrid and Mårtensson, Linda and Cox, Kerry L and Kovacek, Mathilda and Ljungars, Anne and Mattson, Jenny and Sundberg, Annika and Vaughan, Andrew T and Shah, Vallari and Smyth, Neil R and Sheth, Bhavwanti and Chan, H T Claude and Li, Zhan-Chun and Williams, Emily L and Manfredi, Giusi and Oldham, Robert J and Mockridge, C Ian and James, Sonya A and Dahal, Lekh N and Hussain, Khiyam and Nilsson, Björn and Verbeek, J Sjef and Juliusson, Gunnar and Hansson, Markus and Jerkeman, Mats and Johnson, Peter W M and Davies, Andrew and Beers, Stephen A and Glennie, Martin J and Frendéus, Björn and Cragg, Mark S}},
  issn         = {{1878-3686}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{473--488}},
  publisher    = {{Cell Press}},
  series       = {{Cancer Cell}},
  title        = {{Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.}},
  url          = {{http://dx.doi.org/10.1016/j.ccell.2015.03.005}},
  doi          = {{10.1016/j.ccell.2015.03.005}},
  volume       = {{27}},
  year         = {{2015}},
}