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

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

doi:10.1016/j.ccell.2015.03.005

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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	473-488
Journal	Cancer Cell
Volume	27
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2015.03.005
Publication status	Published - 2015

Bibliographical note

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.

Subject classification (UKÄ)

Cancer and Oncology

Access to Document

10.1016/j.ccell.2015.03.005

http://www.ncbi.nlm.nih.gov/pubmed/25873171?dopt=Abstract

Cite this

Roghanian, A., Teige, I., Mårtensson, L., Cox, K. L., Kovacek, M., Ljungars, A., Mattson, J., Sundberg, A., Vaughan, A. T., Shah, V., Smyth, N. R., Sheth, B., Chan, H. T. C., Li, Z-C., Williams, E. L., Manfredi, G., Oldham, R. J., Mockridge, C. I., James, S. A., ... Cragg, M. S. (2015). Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo. Cancer Cell, 27(4), 473-488. https://doi.org/10.1016/j.ccell.2015.03.005

@article{23ee3f4d53454d96b34e6c21ef067e22,

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

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 = "Ali Roghanian and Ingrid Teige and Linda M{\aa}rtensson and Cox, {Kerry L} and Mathilda Kovacek and Anne Ljungars and Jenny Mattson and Annika Sundberg and Vaughan, {Andrew T} and Vallari Shah and Smyth, {Neil R} and Bhavwanti Sheth and Chan, {H T Claude} and Zhan-Chun Li and Williams, {Emily L} and Giusi Manfredi and Oldham, {Robert J} and Mockridge, {C Ian} and James, {Sonya A} and Dahal, {Lekh N} and Khiyam Hussain and Bj{\"o}rn Nilsson and Verbeek, {J Sjef} and Gunnar Juliusson and Markus Hansson and Mats Jerkeman and Johnson, {Peter W M} and Andrew Davies and Beers, {Stephen A} and Glennie, {Martin J} and Bj{\"o}rn Frend{\'e}us and Cragg, {Mark S}",

note = "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, Malm{\"o} (013031300), Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019) Department affilation moved from v1000588 (Tumour Biology, Malm{\"o}) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:28.",

year = "2015",

doi = "10.1016/j.ccell.2015.03.005",

language = "English",

volume = "27",

pages = "473--488",

journal = "Cancer Cell",

issn = "1878-3686",

publisher = "Cell Press",

number = "4",

}

Roghanian, A, Teige, I, Mårtensson, L, Cox, KL, Kovacek, M, Ljungars, A, Mattson, J, Sundberg, A, Vaughan, AT, Shah, V, Smyth, NR, Sheth, B, Chan, HTC, Li, Z-C, Williams, EL, Manfredi, G, Oldham, RJ, Mockridge, CI, James, SA, Dahal, LN, Hussain, K, Nilsson, B, Verbeek, JS, Juliusson, G , Hansson, M , Jerkeman, M, Johnson, PWM, Davies, A, Beers, SA, Glennie, MJ, Frendéus, B & Cragg, MS 2015, 'Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.', Cancer Cell, vol. 27, no. 4, pp. 473-488. https://doi.org/10.1016/j.ccell.2015.03.005

TY - JOUR

T1 - Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.

AU - Roghanian, Ali

AU - Teige, Ingrid

AU - Mårtensson, Linda

AU - Cox, Kerry L

AU - Kovacek, Mathilda

AU - Ljungars, Anne

AU - Mattson, Jenny

AU - Sundberg, Annika

AU - Vaughan, Andrew T

AU - Shah, Vallari

AU - Smyth, Neil R

AU - Sheth, Bhavwanti

AU - Chan, H T Claude

AU - Li, Zhan-Chun

AU - Williams, Emily L

AU - Manfredi, Giusi

AU - Oldham, Robert J

AU - Mockridge, C Ian

AU - James, Sonya A

AU - Dahal, Lekh N

AU - Hussain, Khiyam

AU - Nilsson, Björn

AU - Verbeek, J Sjef

AU - Juliusson, Gunnar

AU - Hansson, Markus

AU - Jerkeman, Mats

AU - Johnson, Peter W M

AU - Davies, Andrew

AU - Beers, Stephen A

AU - Glennie, Martin J

AU - Frendéus, Björn

AU - Cragg, Mark S

N1 - 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.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1016/j.ccell.2015.03.005

DO - 10.1016/j.ccell.2015.03.005

M3 - Article

C2 - 25873171

SN - 1878-3686

VL - 27

SP - 473

EP - 488

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

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

Abstract

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