Cytotoxicity of cytokine-induced killer cells targeted by a bispecific antibody to gastric cancer cells

Oncol Lett. 2013 Jun;5(6):1826-1832. doi: 10.3892/ol.2013.1281. Epub 2013 Apr 2.

Abstract

The aim of the present study was to investigate the cytotoxic activity of cytokine-induced killer (CIK) cells targeted by an epidermal growth factor receptor (EGFR)/CD3 bispecific antibody (BsAb) to the gastric cancer cell line SGC7901. A BsAb was constructed by chemically cross-linking a monoclonal antibody (McAb) against human CD3 with another McAb against human EGFR. An immunocytochemistry assay was performed to detect the expression of EGFR in SGC7901 cells. The cytotoxic activity of CIK cells targeted by the EGFR/CD3 BsAb was analyzed by the 51Cr release assay, Subsequently, a comparison of the cytotoxic activity between CIK cells targeted by EGFR/CD3 BsAb, CIK cells targeted by EGFR McAb or/and CD3 McAb and CIK cells was performed. The antineoplastic activity of the CIK cells directed using the EGFR/CD3 BsAb in vivo was analyzed by tumor growth and tumor reduction assays. The cell lysis rate of CIK cells targeted by the EGFR/CD3 BsAb was higher compared with those of CIK cells targeted by CD3 McAb only or by CD3 McAb and EGFR McAb. The lysis rates of the latter two groups were significantly higher than those of CIK cells targeted by EGFR McAb only and CIK cells (P<0.05). The mean tumor reduction using the administration of CIK cells directed by the EGFR/CD3 BsAb was higher than those of the other groups (P<0.05). The results indicate that the EGFR/CD3 BsAb is able to enhance the ability of CIK cells to bind to and kill gastric cancer cells in vitro and in vivo.

Keywords: bispecific antibody; cytokine-induced killer cell; gastric cancer; immunotherapy.