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Antagonistic human FcyRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo

Antagonistic human FcyRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo
Antagonistic human FcyRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo
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) Fc?RIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. Fc?RIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFc?RIIB-transgenic (Tg) mice, Fc?RIIB-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 hFc?RIIB antibodies for clinical assessment.
1535-6108
473-488
Roghanian, Ali
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Teige, Ingrid
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Mårtensson, Linda
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Cox, Kerry L.
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Kovacek, Mathilda
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Ljungars, Anne
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Mattson, Jenny
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Sundberg, Annika
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Vaughan, Andrew T.
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Shah, Vallari
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Smyth, Neil R.
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Sheth, Bhavwanti
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Chan, H.T. Claude
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Li, Zhan-Chun
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Williams, Emily L.
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Manfredi, Giusi
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Oldham, Robert J.
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James, Sonya A.
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Dahal, Lekh N.
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Nilsson, Björn
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Verbeek, J. Sjef
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Juliusson, Gunnar
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Hansson, Markus
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Jerkeman, Mats
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Johnson, Peter W.M.
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Davies, Andrew
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Beers, Stephen A.
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Glennie, Martin J.
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Frendéus, Björn
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Cragg, Mark S.
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Roghanian, Ali
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Teige, Ingrid
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Mårtensson, Linda
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Cox, Kerry L.
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Ljungars, Anne
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Mattson, Jenny
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Sundberg, Annika
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Vaughan, Andrew T.
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Shah, Vallari
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Chan, H.T. Claude
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Williams, Emily L.
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Manfredi, Giusi
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Oldham, Robert J.
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Mockridge, C. Ian
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James, Sonya A.
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Dahal, Lekh N.
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Hussain, Khiyam
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Nilsson, Björn
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Verbeek, J. Sjef
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Juliusson, Gunnar
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Hansson, Markus
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Jerkeman, Mats
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Johnson, Peter W.M.
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Davies, Andrew
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Glennie, Martin J.
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Cragg, Mark S.
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Roghanian, Ali, Teige, Ingrid, Mårtensson, Linda, Cox, Kerry L., Kovacek, Mathilda, Ljungars, Anne, Mattson, Jenny, Sundberg, Annika, Vaughan, Andrew T., Shah, Vallari, Smyth, Neil R., Sheth, Bhavwanti, Chan, H.T. Claude, Li, Zhan-Chun, Williams, Emily L., Manfredi, Giusi, Oldham, Robert J., Mockridge, C. Ian, James, Sonya A., Dahal, Lekh N., Hussain, Khiyam, Nilsson, Björn, Verbeek, J. Sjef, Juliusson, Gunnar, Hansson, Markus, Jerkeman, Mats, Johnson, Peter W.M., Davies, Andrew, Beers, Stephen A., Glennie, Martin J., Frendéus, Björn and Cragg, Mark S. (2015) Antagonistic human FcyRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo. Cancer Cell, 27 (4), 473-488. (doi:10.1016/j.ccell.2015.03.005). (PMID:25873171)

Record type: Article

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) Fc?RIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. Fc?RIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFc?RIIB-transgenic (Tg) mice, Fc?RIIB-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 hFc?RIIB antibodies for clinical assessment.

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Accepted/In Press date: 10 March 2015
e-pub ahead of print date: 13 April 2015
Published date: 13 April 2015
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 376434
URI: http://eprints.soton.ac.uk/id/eprint/376434
DOI: doi:10.1016/j.ccell.2015.03.005
ISSN: 1535-6108
PURE UUID: fef8fb1a-34fe-4a31-ba03-632273d841f2
ORCID for Ali Roghanian: ORCID iD orcid.org/0000-0003-1316-4218
ORCID for Andrew T. Vaughan: ORCID iD orcid.org/0000-0001-6076-3649
ORCID for H.T. Claude Chan: ORCID iD orcid.org/0000-0003-0530-9480
ORCID for Peter W.M. Johnson: ORCID iD orcid.org/0000-0003-2306-4974
ORCID for Andrew Davies: ORCID iD orcid.org/0000-0002-7517-6938
ORCID for Stephen A. Beers: ORCID iD orcid.org/0000-0002-3765-3342
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 28 Apr 2015 12:51
Last modified: 15 Mar 2024 03:34

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Contributors

Author: Ali Roghanian ORCID iD
Author: Ingrid Teige
Author: Linda Mårtensson
Author: Kerry L. Cox
Author: Mathilda Kovacek
Author: Anne Ljungars
Author: Jenny Mattson
Author: Annika Sundberg
Author: Andrew T. Vaughan ORCID iD
Author: Vallari Shah
Author: Neil R. Smyth
Author: Bhavwanti Sheth
Author: H.T. Claude Chan ORCID iD
Author: Zhan-Chun Li
Author: Emily L. Williams
Author: Giusi Manfredi
Author: Robert J. Oldham
Author: C. Ian Mockridge
Author: Sonya A. James
Author: Lekh N. Dahal
Author: Khiyam Hussain
Author: Björn Nilsson
Author: J. Sjef Verbeek
Author: Gunnar Juliusson
Author: Markus Hansson
Author: Mats Jerkeman
Author: Peter W.M. Johnson ORCID iD
Author: Andrew Davies ORCID iD
Author: Stephen A. Beers ORCID iD
Author: Martin J. Glennie
Author: Björn Frendéus
Author: Mark S. Cragg ORCID iD

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