A NEW ANTI-TUMOR IMMUNOTHERAPY TARGETING HUMAN PROTO-ONCOGENE PRODUCT

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To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody(BSAb)containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BSAb specifically reacts with both c-erbB-2-positive tumor cells and CD3^+CTL.Human CD4^+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4^+ helper/killer cells with the BSAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4^+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BSAb. Moreover, by combination with the BSAb, CD4^+ helper/killer cells showed a significant in vivo anti-tumor effect against c-erbB-2 positive human cancer cells in severe combined immunodeficiency mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BSAb-directed adoptive tumor immunotherapy. Thus, we have established a large-scale culture system of these CD4^+ helper/killer T cells to provide enough number of the cells for future clinical trials.