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

doi:10.3390/ijms18091797

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

Rusheni Munisvaradass

¹,

Suresh Kumar

^2,3

Chandramohan Govindasamy

⁴,

Khalid S. Alnumair

⁴ and

Pooi Ling Mok

^1,2,*

Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Genetics and Regenerative Medicine Research Center, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

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.

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

Received: 20 May 2017 / Revised: 8 August 2017 / Accepted: 9 August 2017 / Published: 8 September 2017

(This article belongs to the Section Biochemistry)

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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

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MDPI and ACS Style

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. https://doi.org/10.3390/ijms18091797

AMA Style

Munisvaradass R, Kumar S, Govindasamy C, Alnumair KS, Mok PL. 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. 2017; 18(9):1797. https://doi.org/10.3390/ijms18091797

Chicago/Turabian Style

Munisvaradass, Rusheni, Suresh Kumar, Chandramohan Govindasamy, Khalid S. Alnumair, and Pooi L. Mok. 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, no. 9: 1797. https://doi.org/10.3390/ijms18091797

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

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