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Specific targeting of in vitro ‐activated human antitumour effector cells using anti‐CD3 × anti‐c‐ erbB ‐2 bispecific antibody
Author(s) -
TSUKAMOTO HIDEO,
NAKAMURA YOSHIHIKO,
MASUKO TAKASHI,
HASHIMOTO YOSHIYUKI,
HABU SONOKO,
NISHIMURA TAKASHI
Publication year - 1993
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1993.11
Subject(s) - cytotoxicity , cd3 , cancer research , cytotoxic t cell , cd8 , immunotherapy , lymphokine , interleukin 2 , in vitro , erbb , chemistry , biology , microbiology and biotechnology , immunology , antigen , immune system , receptor , biochemistry
Summary Bispecific antibody (BSAb) consisting of anti‐CD3 plus anti‐ c‐cerbB ‐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 × 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, γδ 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.