Abstract
The KM231 mAb recognizing sialyl Lewis a (sLe a) epitope of glycoprotein or glycolipid expressed on various human cancers was used to prepare bispecific antibody (BSAb) containing anti-CD3 × anti-sLe a mAb. The effect of anti-CD3 × anti-sLe a BSAb on the induction of cytotoxicity by activated T cells was investigated. The activated CD3 + T cells expressing CD8 or CD4 were induced from human peripheral blood mononuclear cells by culture with recombinant IL-2 plus immobilized anti-CD3 mAb. The activated CD8 + and CD4 + T cells showed marginal cytotoxicity against tumor cells by themselves. However, addition of anti-CD3 × anti-sLe a BSAb resulted in a great augmentation of their cytotoxicity against gastrointestinal tumor cells. The BSAb also triggered IL-2 production of CD4 + helper/killer T cells during lysis of tumor cells. Moreover, the BSAb was demonstrated to have a potent in vivo antitumor activity against human colon cancer implanted in nude mice by combination with CD4 + helper/killer cells. These results demonstrated that sLe a antigen might be a good target molecule for BSAb-directed adoptive tumor immunotherapy.
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