Bispecific anti‑CD3 x anti‑HER2 antibody mediates T cell cytolytic activity to HER2‑positive colorectal cancer in vitro and in vivo

Han,Huamin; Ma,Juan; Zhang,Keming; Li,Wei; Liu,Changzhen; Zhang,Yu; Zhang,Ganlin; Ma,Pan; Wang,Lei; Zhang,Ge; Tao,Hua; Gao,Bin

doi:10.3892/ijo.2014.2663

Bispecific anti‑CD3 x anti‑HER2 antibody mediates T cell cytolytic activity to HER2‑positive colorectal cancer in vitro and in vivo

Authors:
- Huamin Han
- Juan Ma
- Keming Zhang
- Wei Li
- Changzhen Liu
- Yu Zhang
- Ganlin Zhang
- Pan Ma
- Lei Wang
- Ge Zhang
- Hua Tao
- Bin Gao
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Affiliations: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China, Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, P.R. China, Department of Oncology, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, Beijing, P.R. China
Published online on: September 18, 2014 https://doi.org/10.3892/ijo.2014.2663
Pages: 2446-2454

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Abstract

Targeting HER2 overexpressed breast cancer cells with anti‑HER2 monoclonal antibodies inhibits tumor growth. Here we investigated whether HER2 can serve as a target for T cell‑mediated immunotherapy of human colorectal carcinoma. Specific cytolytic activity of activated T cells (ATCs) armed with anti‑CD3 x anti‑HER2 bispecific antibody (HER2Bi‑Ab) against HER2+ tumor cells was evaluated by bioluminescent signal generated by luciferase reporter on tumor cells in vitro and in vivo. In contrast to unarmed ATCs, increased cytotoxic activity of HER2Bi‑armed ATCs against HER2+ tumor cells was observed. Moreover, HER2Bi‑armed ATCs expressed higher level of activation marker CD69 and secreted significantly higher levels of IFN‑γ than the unarmed ATC counterpart. In addition, compared with anti‑HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi‑armed ATCs showed significant suppression against colorectal carcinoma cells. In colorectal tumor cell xenograft mice, infusion of HER2Bi‑armed ATCs successfully inhibited the growth of Colo205‑luc cells. The HER2Bi‑armed ATCs with anti‑tumor effects may provide a promising immunotherapy for colorectal carcinoma in the future.

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