Cargando…

Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressiv...

Descripción completa

Detalles Bibliográficos
Autores principales: Munisvaradass, Rusheni, Kumar, Suresh, Govindasamy, Chandramohan, Alnumair, Khalid S., Mok, Pooi Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618474/
https://www.ncbi.nlm.nih.gov/pubmed/28885562
http://dx.doi.org/10.3390/ijms18091797
_version_ 1783267194432389120
author Munisvaradass, Rusheni
Kumar, Suresh
Govindasamy, Chandramohan
Alnumair, Khalid S.
Mok, Pooi Ling
author_facet Munisvaradass, Rusheni
Kumar, Suresh
Govindasamy, Chandramohan
Alnumair, Khalid S.
Mok, Pooi Ling
author_sort Munisvaradass, Rusheni
collection PubMed
description Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non–transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours.
format Online
Article
Text
id pubmed-5618474
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-56184742017-09-30 Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells Munisvaradass, Rusheni Kumar, Suresh Govindasamy, Chandramohan Alnumair, Khalid S. Mok, Pooi Ling Int J Mol Sci Article Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non–transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours. MDPI 2017-09-08 /pmc/articles/PMC5618474/ /pubmed/28885562 http://dx.doi.org/10.3390/ijms18091797 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Munisvaradass, Rusheni
Kumar, Suresh
Govindasamy, Chandramohan
Alnumair, Khalid S.
Mok, Pooi Ling
Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells
title Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells
title_full Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells
title_fullStr Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells
title_full_unstemmed Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells
title_short Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells
title_sort human cd3+ t-cells with the anti-erbb2 chimeric antigen receptor exhibit efficient targeting and induce apoptosis in erbb2 overexpressing breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618474/
https://www.ncbi.nlm.nih.gov/pubmed/28885562
http://dx.doi.org/10.3390/ijms18091797
work_keys_str_mv AT munisvaradassrusheni humancd3tcellswiththeantierbb2chimericantigenreceptorexhibitefficienttargetingandinduceapoptosisinerbb2overexpressingbreastcancercells
AT kumarsuresh humancd3tcellswiththeantierbb2chimericantigenreceptorexhibitefficienttargetingandinduceapoptosisinerbb2overexpressingbreastcancercells
AT govindasamychandramohan humancd3tcellswiththeantierbb2chimericantigenreceptorexhibitefficienttargetingandinduceapoptosisinerbb2overexpressingbreastcancercells
AT alnumairkhalids humancd3tcellswiththeantierbb2chimericantigenreceptorexhibitefficienttargetingandinduceapoptosisinerbb2overexpressingbreastcancercells
AT mokpooiling humancd3tcellswiththeantierbb2chimericantigenreceptorexhibitefficienttargetingandinduceapoptosisinerbb2overexpressingbreastcancercells