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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2017
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| Online Access: | http://psasir.upm.edu.my/id/eprint/15069/ http://psasir.upm.edu.my/id/eprint/15069/1/15069.pdf |
| _version_ | 1848842573585580032 |
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| author | Munisvaradass, Rusheni Subbiah, Suresh Kumar Govindasamy, Chandramohan Alnumair, Khalid S. Mok, Pooi Ling |
| author_facet | Munisvaradass, Rusheni Subbiah, Suresh Kumar Govindasamy, Chandramohan Alnumair, Khalid S. Mok, Pooi Ling |
| author_sort | Munisvaradass, Rusheni |
| building | UPM Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-15T08:01:17Z |
| format | Article |
| id | upm-15069 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T08:01:17Z |
| publishDate | 2017 |
| publisher | MDPI AG |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-150692019-05-09T01:22:49Z http://psasir.upm.edu.my/id/eprint/15069/ 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 Subbiah, Suresh Kumar Govindasamy, Chandramohan Alnumair, Khalid S. Mok, Pooi Ling 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 AG 2017 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/15069/1/15069.pdf Munisvaradass, Rusheni and Subbiah, Suresh Kumar and Govindasamy, Chandramohan and Alnumair, Khalid S. and Mok, Pooi Ling (2017) Human CD3+ T-cells with the anti-ERBB2 chimeric antigen receptor exhibit efficient targeting and induce apoptosis in ERBB2 overexpressing breast cancer cells. International Journal of Molecular Sciences, 18 (9). art. no. 1797. pp. 1-16. ISSN 1422-0067 https://www.mdpi.com/1422-0067/18/9/1797 10.3390/ijms18091797 |
| spellingShingle | Munisvaradass, Rusheni Subbiah, Suresh Kumar 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 |
| url | http://psasir.upm.edu.my/id/eprint/15069/ http://psasir.upm.edu.my/id/eprint/15069/ http://psasir.upm.edu.my/id/eprint/15069/ http://psasir.upm.edu.my/id/eprint/15069/1/15069.pdf |