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.
Tsukamoto
H
H
Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Nakamura
Y
Y
Masuko
T
T
Hashimoto
Y
Y
Habu
S
S
Nishimura
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D000912:Antibodies, Neoplasm / Q000302:isolation & purification; D000918:Antibody Specificity; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D066298:In Vitro Techniques; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D017252:CD3 Complex; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases