Targeting bladder cancer using activated T cells armed with bispecific antibodies

Ma,Juan; Ge,Jing; Xue,Xin; Xiu,Weigang; Ma,Pan; Sun,Ximing; Zhang,Man

doi:10.3892/or.2018.6211

Targeting bladder cancer using activated T cells armed with bispecific antibodies

Authors:
- Juan Ma
- Jing Ge
- Xin Xue
- Weigang Xiu
- Pan Ma
- Ximing Sun
- Man Zhang
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Affiliations: Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China, Department of Immunology, China Basic Medical Theory of Chinese Medicine, Academy of Chinese Medical Sciences, Beijing 100700, P.R. China, Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China
Published online on: January 11, 2018 https://doi.org/10.3892/or.2018.6211
Pages: 1245-1252

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Abstract

In the present study, we aimed to investigate whether EGFR or HER2 may serve as a target for T cell-mediated immunotherapy against human bladder cancer. Expression of EGFR and HER2 was detected on the surface of bladder cancer cells, including Pumc-91 and T24 cells, and their chemotherapeutic drug-resistant counterparts. Activated T cells (ATCs) were generated from healthy PBMCs that were stimulated by the combination of anti-CD3 monoclonal antibody and anti‑CD28 monoclonal antibody in the presence of interleukin-2 for 14 days. The ATCs were then armed with chemically hetero-conjugated anti-CD3xanti-EGFR (EGFRBi-Ab) or anti-CD3xanti-HER2 (HER2Bi-Ab). The specific cytolytic activity of ATCs armed with EGFRBi-Ab or HER2Bi-Ab against human bladder cancer cells was evaluated by lactate dehydrogenase activity assays in vitro. In contrast to unarmed ATCs, EGFRBi-Ab-armed ATCs and HER2Bi-Ab-armed ATCs showed increased cytotoxic activity against bladder cancer cells. Moreover, Bi-Ab-armed ATCs expressed higher levels of activating marker CD69 and secreted more IFN-γ, TNF-α and IL-2 than did unarmed ATCs. EGFRBi-Ab- or HER2Bi-Ab-armed ATCs may provide a promising immunotherapy for bladder cancer.

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