Open AccessBispecific anti-CD3 x anti-HER2 antibody mediates T cell cytolytic activity to HER2-positive colorectal cancer in vitro and in vivo
Author(s) -
Houxiang Han,
Juan Ma,
Keming Zhang,
Wei Li,
Changzhen Liu,
Yu Zhang,
GanLin Zhang,
Pan Ma,
Lei Wang,
Ge Zhang,
Hua Tao,
Bin Gao
Publication year - 2014
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2014.2663
Subject(s) - cancer research , cytotoxic t cell , colorectal cancer , in vivo , immunotherapy , antibody , cancer , monoclonal antibody , oncogene , cytolysis , medicine , biology , in vitro , immunology , cell cycle , biochemistry , microbiology and biotechnology
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.