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
  • View Affiliations

  • 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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December-2014
Volume 45 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Han H, Ma J, Zhang K, Li W, Liu C, Zhang Y, Zhang G, Ma P, Wang L, Zhang G, Zhang G, et al: Bispecific anti‑CD3 x anti‑HER2 antibody mediates T cell cytolytic activity to HER2‑positive colorectal cancer in vitro and in vivo. Int J Oncol 45: 2446-2454, 2014.
APA
Han, H., Ma, J., Zhang, K., Li, W., Liu, C., Zhang, Y. ... Gao, B. (2014). Bispecific anti‑CD3 x anti‑HER2 antibody mediates T cell cytolytic activity to HER2‑positive colorectal cancer in vitro and in vivo. International Journal of Oncology, 45, 2446-2454. https://doi.org/10.3892/ijo.2014.2663
MLA
Han, H., Ma, J., Zhang, K., Li, W., Liu, C., Zhang, Y., Zhang, G., Ma, P., Wang, L., Zhang, G., Tao, H., Gao, B."Bispecific anti‑CD3 x anti‑HER2 antibody mediates T cell cytolytic activity to HER2‑positive colorectal cancer in vitro and in vivo". International Journal of Oncology 45.6 (2014): 2446-2454.
Chicago
Han, H., Ma, J., Zhang, K., Li, W., Liu, C., Zhang, Y., Zhang, G., Ma, P., Wang, L., Zhang, G., Tao, H., Gao, B."Bispecific anti‑CD3 x anti‑HER2 antibody mediates T cell cytolytic activity to HER2‑positive colorectal cancer in vitro and in vivo". International Journal of Oncology 45, no. 6 (2014): 2446-2454. https://doi.org/10.3892/ijo.2014.2663