OK432-activated natural killer cells enhanced trastuzumab (Herceptin)-mediated antibody-dependent cellular cytotoxicity in patients with advanced cancer.
BACKGROUND
Adoptive immunotherapy using natural killer (NK) cells from cancer patients yielded only modest success. Whether Herceptin and OK432-activated NK cells (NK cells obtained by stimulating peripheral blood mononuclear cells with OK432 and interleukin-2) improve the outcome of adoptive immunotherapy against HER-2/neu positive tumor cells via antibody-dependent cellular cytotoxicity, was examined in vitro.


METHODS
A 51Cr release assay was performed to assess cytotoxicity. OK432-activated NK cells and lymphokine-activated killer (LAK) cells from healthy donors and cancer patients were used as effectors. Three cell lines expressing different amounts of HER-2/neu served as targets.


RESULTS
In the case of effectors from patients, OK432-activated NK cells showed higher cytotoxicity than that of LAK cells, and the cytotoxicity of OK432-activated NK cells against the SK-BR-3 cell line (over-expressing HER-2/neu) was increased by Herceptin.


CONCLUSIONS
Combination of Herceptin and OK432-activeted NK cells may improve the efficacy of the treatment for HER-2/neu-positive malignancy.
Sudo
Toshimi
T
Department of Gastrointerological Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. sudomako@yahoo.co.jp
Aruga
Atsushi
A
Shimizu
Koichi
K
Matsushita
Norimasa
N
Takasaki
Ken
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D010844:Picibanil / Q000494:pharmacology*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010844:Picibanil; D007371:Interferon-gamma; D000068878:Trastuzumab