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

Targeting HER 2 overexpressed breast cancer cells with anti-HER 2 monoclonal antibodies inhibits tumor growth. Here we investigated whether HER 2 can serve as a target for T-cell.mediated immunotherapy of human colorectal carcinoma. Specific cytolytic activity of activated T-cells (ATC s) armed with anti-C D3 × anti-HER 2 bispecific antibody (HER 2Bi-A b) against HER 2+ tumor cells was evaluated by bioluminescent signal generated by luciferase reporter on tumor cells in vitro and in vivo. In contrast to unarmed ATC s, increased cytotoxic activity of HER 2Bi-armed ATC s against HER 2+ tumor cells was observed. Moreover, HER 2Bi-armed ATC s 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-HER 2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATCs showed significant suppression against colorectal carcinoma cells. In colorectal tumor cell xenograft mice, infusion of HER 2Bi-armed ATC s successfully inhibited the growth of Colo205.luc cells. The HER 2Bi-armed ATC s with anti-tumor effects may provide a promising immunotherapy for colorectal carcinoma in the future.