Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer

gC1qR is highly expressed in breast cancer and plays a role in cancer cell proliferation. This study explored therapy with gC1qR monoclonal antibody 60.11, directed against the C1q binding domain of gC1qR, in a murine orthotopic xenotransplant model of triple negative breast cancer. MDA231 breast ca...

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Main Authors: Ellinor I. Peerschke, Elisa de Stanchina, Qing Chang, Katia Manova-Todorova, Afsar Barlas, Anne G. Savitt, Brian V. Geisbrecht, Berhane Ghebrehiwet
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Antibodies
Subjects:
Online Access:https://www.mdpi.com/2073-4468/9/4/51
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spelling doaj-b3bfd026ac4f49ce814d26f8b134bf752020-11-25T03:58:22ZengMDPI AGAntibodies2073-44682020-10-019515110.3390/antib9040051Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast CancerEllinor I. Peerschke0Elisa de Stanchina1Qing Chang2Katia Manova-Todorova3Afsar Barlas4Anne G. Savitt5Brian V. Geisbrecht6Berhane Ghebrehiwet7Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USASloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USASloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USASloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USASloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506, USADepartments of Medicine and Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USAgC1qR is highly expressed in breast cancer and plays a role in cancer cell proliferation. This study explored therapy with gC1qR monoclonal antibody 60.11, directed against the C1q binding domain of gC1qR, in a murine orthotopic xenotransplant model of triple negative breast cancer. MDA231 breast cancer cells were injected into the mammary fat pad of athymic nu/nu female mice. Mice were segregated into three groups (<i>n</i> = 5, each) and treated with the vehicle (group 1) or gC1qR antibody 60.11 (100 mg/kg) twice weekly, starting at day 3 post-implantation (group 2) or when the tumor volume reached 100 mm<sup>3</sup> (group 3). At study termination (d = 35), the average tumor volume in the control group measured 895 ± 143 mm<sup>3</sup>, compared to 401 ± 48 mm<sup>3</sup> and 701 ± 100 mm<sup>3</sup> in groups 2 and 3, respectively (<i>p</i> < 0.05). Immunohistochemical staining of excised tumors revealed increased apoptosis (caspase 3 and TUNEL staining) in 60.11-treated mice compared to controls, and decreased angiogenesis (CD31 staining). Slightly decreased white blood cell counts were noted in 60.11-treated mice. Otherwise, no overt toxicities were observed. These data are the first to demonstrate an in vivo anti-tumor effect of 60.11 therapy in a mouse model of triple negative breast cancer.https://www.mdpi.com/2073-4468/9/4/51gC1qRbreast cancerxenotransplant model
collection DOAJ
language English
format Article
sources DOAJ
author Ellinor I. Peerschke
Elisa de Stanchina
Qing Chang
Katia Manova-Todorova
Afsar Barlas
Anne G. Savitt
Brian V. Geisbrecht
Berhane Ghebrehiwet
spellingShingle Ellinor I. Peerschke
Elisa de Stanchina
Qing Chang
Katia Manova-Todorova
Afsar Barlas
Anne G. Savitt
Brian V. Geisbrecht
Berhane Ghebrehiwet
Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer
Antibodies
gC1qR
breast cancer
xenotransplant model
author_facet Ellinor I. Peerschke
Elisa de Stanchina
Qing Chang
Katia Manova-Todorova
Afsar Barlas
Anne G. Savitt
Brian V. Geisbrecht
Berhane Ghebrehiwet
author_sort Ellinor I. Peerschke
title Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer
title_short Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer
title_full Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer
title_fullStr Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer
title_full_unstemmed Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer
title_sort anti gc1qr/p32/habp1 antibody therapy decreases tumor growth in an orthotopic murine xenotransplant model of triple negative breast cancer
publisher MDPI AG
series Antibodies
issn 2073-4468
publishDate 2020-10-01
description gC1qR is highly expressed in breast cancer and plays a role in cancer cell proliferation. This study explored therapy with gC1qR monoclonal antibody 60.11, directed against the C1q binding domain of gC1qR, in a murine orthotopic xenotransplant model of triple negative breast cancer. MDA231 breast cancer cells were injected into the mammary fat pad of athymic nu/nu female mice. Mice were segregated into three groups (<i>n</i> = 5, each) and treated with the vehicle (group 1) or gC1qR antibody 60.11 (100 mg/kg) twice weekly, starting at day 3 post-implantation (group 2) or when the tumor volume reached 100 mm<sup>3</sup> (group 3). At study termination (d = 35), the average tumor volume in the control group measured 895 ± 143 mm<sup>3</sup>, compared to 401 ± 48 mm<sup>3</sup> and 701 ± 100 mm<sup>3</sup> in groups 2 and 3, respectively (<i>p</i> < 0.05). Immunohistochemical staining of excised tumors revealed increased apoptosis (caspase 3 and TUNEL staining) in 60.11-treated mice compared to controls, and decreased angiogenesis (CD31 staining). Slightly decreased white blood cell counts were noted in 60.11-treated mice. Otherwise, no overt toxicities were observed. These data are the first to demonstrate an in vivo anti-tumor effect of 60.11 therapy in a mouse model of triple negative breast cancer.
topic gC1qR
breast cancer
xenotransplant model
url https://www.mdpi.com/2073-4468/9/4/51
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