HER2-specific cytotoxic activity of lymphokine-activated killer cells in the presence of trastuzumab.
We investigated whether trastuzumab, a humanized anti-HER2 monoclonal antibody, could induce HER2-specific cytotoxic activity on lymphokine-activated killer (LAK) cells. Trastuzumab alone was not toxic to the HER2-positive breast cancer cell lines MDA-MB453 and ZR75-1, nor to the HER2-negative breast cancer cell lines MDA-MB468 and MCF-7. LAK cells, which were activated with 1000 U/ml IL-2 for 4 days (4-day LAK), showed cytotoxic activity against the MDA-MB453, ZR75-1 and MCF-7 cells, but not against MDA-MB468 cells. LAK cell cytotoxic activity against the HER2-positive breast cancer cell lines MDA-MB453 and ZR75-1 was significantly augmented in the presence of 10 nM trastuzumab, but that against the HER2-negative breast cancer cell lines MDA-MB468 and MCF-7 was not. The cytotoxic activity of LAK cells plus trastuzumab against the MDA-MB453 cells was significantly inhibited by the addition of cold MDA-MB453 cells or cold ZR75-1 cells, but not by addition of cold MDA-MB468 cells. Twenty-nine percent of the 4-day LAK cells were CD16+, and the cytotoxicity of LAK cells plus trastuzumab was abrogated with the anti-CD16 antibody treatment of the LAK cells in the cytotoxicity assay. Only 7% of the 10-day LAK cells were CD16+, and the 10-day LAK cells failed to exhibit cytotoxicity even with trastuzumab. These results suggest that HER2-specific cytotoxic activity, which is mediated by an antibody-dependent cellular cytotoxicity (ADCC) mechanism, can be induced on LAK cells by the addition of trastuzumab.
Yamaguchi
Yoshiyuki
Y
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan. shogo@hiroshima-u.ac.jp
Hironaka
Katsuji
K
Okawaki
Makoto
M
Okita
Riki
R
Matsuura
Kazuo
K
Ohshita
Akiko
A
Toge
Tetsuya
T
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D011961:Receptors, Fc; D017452:Receptors, IgG; D000068878:Trastuzumab