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Int. J. Mol. Sci. 2017, 18(9), 1797; doi:10.3390/ijms18091797

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

1
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
2
Genetics and Regenerative Medicine Research Center, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
3
Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
4
Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
*
Author to whom correspondence should be addressed.
Received: 20 May 2017 / Revised: 8 August 2017 / Accepted: 9 August 2017 / Published: 8 September 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: breast cancer; chimeric antigen receptor (CAR); human epidermal growth factor receptor (ERBB2); immunotherapy; transduction; human T-cells breast cancer; chimeric antigen receptor (CAR); human epidermal growth factor receptor (ERBB2); immunotherapy; transduction; human T-cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Munisvaradass, R.; Kumar, S.; Govindasamy, C.; Alnumair, K.S.; Mok, P.L. Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells. Int. J. Mol. Sci. 2017, 18, 1797.

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