Specific targeting of in vitro-activated human antitumour effector cells using anti-CD3 x anti-c-erbB-2 bispecific antibody.

Bispecific antibody (BSAb) consisting of anti-CD3 plus anti-c-erbB-2 Fab fragments for the application to adoptive tumour immunotherapy was prepared. This bifunctional hetero-F(ab')2 antibody reacted with both human CD3+ T cells and c-erbB-2 positive human tumour cells. Human CD8+ T cells activated with immobilized anti-CD3 plus interleukin 2 showed marginal cytotoxicity against tumour cells. However, addition of the prepared BSAb into the culture resulted in a marked augmentation of the cytotoxicity by the activated CD8+ T cells in a dose-dependent manner. The enhanced cytotoxicity of CD8+ T cells in the presence of BSAb was specific for c-erbB-2 positive tumour cells. Moreover, it was demonstrated that anti-CD3 x anti-c-erbB-2 BSAb was also effective for the specific targeting of various kinds of in vitro-activated antitumour effector cells such as lymphokine-activated killer cells, CD4+ helper/killer cells, gamma delta T cells and activated tumour-infiltrating CD8+ T cells. These results indicated that BSAb consisted of anti-CD3 and anti-c-erbB-2 will become a useful tool for the adoptive tumour immunotherapy of human cancer expressing c-erbB-2 oncogene products.