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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; 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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published
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Cancer Cell
volume
27
issue
4
pages
473 - 488
publisher
Cell Press
external identifiers
  • pmid:25873171
  • wos:000352962600010
  • scopus:84928005736
ISSN
1878-3686
DOI
10.1016/j.ccell.2015.03.005
language
English
LU publication?
yes
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23ee3f4d-5345-4d96-b34e-6c21ef067e22 (old id 5341867)
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http://www.ncbi.nlm.nih.gov/pubmed/25873171?dopt=Abstract
date added to LUP
2015-05-05 20:07:07
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2017-10-22 03:26:47
@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},
  volume       = {27},
  year         = {2015},
}