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Human C‐ERBB ‐2 proto‐oncogene product as a target for bispecific‐antibody‐directed adoptive tumor immunotherapy
Author(s) -
Nishimura Takashi,
Nakamura Yoshihiko,
Tsukamoto Hideo,
Takeuchi Yasuhiro,
Tokuda Yutaka,
Iwasawa Megumi,
Yamamoto Tadashi,
Masuko Takashi,
Hashimoto Yoshiyuki,
Habu Sonoko
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910500523
Subject(s) - immunotherapy , cancer research , ctl* , monoclonal antibody , cd3 , cytotoxicity , adoptive cell transfer , peripheral blood mononuclear cell , cytotoxic t cell , cancer immunotherapy , erbb , lymphokine activated killer cell , immunology , antibody , biology , cancer , interleukin 21 , immune system , t cell , cd8 , in vitro , biochemistry , genetics
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 (MAb) 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 strong in vivo anti‐tumor effect against c‐ erbB ‐2 transfectant or human colon‐cancer cells implanted in nude 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.