Retargeting of killer cells with bispecific antibodies greatly enchances MUC1 specific cytotoxicity

For the purpose of establishing a new effective adoptive immunotherapy, we synthesized two bispecific antibodies (BsAbs), MUC1 x CD3 BsAb constructed with MUSE11 (anti MUC1) and OKT3; and MUC1 x CD28 BsAB constructed with MUSE11 and 15E8 (anti CD28) antibodies. These two BsAbs reacted well with tumor (TFK 1) and LAK cells. When 2 x 10⁷ LAK cells sensitized with both kinds of BsAbs were administered intravenously to TFK 1 grafted SCID mice (tumor size 5 mm), inhibition of tumor growth was clearly observed. In order to obtain effective vaccine cells, we transfected MUC1 gene to EBV lymphoblastoid cells. The established vaccine cells induced highly active killer cells in the autologous MLTC. Thus, we suggest vaccine combined specific targeting therapy using the two kinds of BsAbs as potential therapy for control of MUC1 positive tumors.