Neoadjuvant immunotherapy enhances radiosensitivity through natural killer cell activation
Journal
Cancer Biotherapy and Radiopharmaceuticals
Journal Volume
25
Journal Issue
1
Pages
39-45
Date Issued
2010
Author(s)
Abstract
We investigated whether natural killer (NK) cells in the tumor microenvironment have a radiosensitization effect. The radiosensitization effect of combined CpG and Herceptin? (Genentech, Inc., South San Francisco, CA) (CpG/Herceptin), given before or after radiation, was evaluated by using a murine colon cancer cell line overexpressing human HER2/neu, CT26HER2/neu. In vitro radiosensitization effects were investigated by coculture of CT26HER2/neu with splenocytes, CpG, and Herceptin before applying radiation. Tumor cells, cocultured with CpG-pretreated splenocytes and Herceptin, were more vulnerable to radiation damage. In BALB/c mice injected with CT26HER2/neu, CpG/Herceptin administered before radiotherapy was associated with a better retardation of tumor growth than when administered after radiotherapy. The radiosensitization effect was significantly abrogated by NK-cell depletion, indicating that NK cells play an essential role in it. Further, surviving mice treated with CpG or CpG/Herceptin and reverse transcriptase were resistant to renewed tumor challenge, suggesting the presence of an induced immune response to the tumor. Neoadjuvant immunotherapy with CpG/Herceptin may improve response to radiotherapy of HER2/neu-expressing tumors. Copyright 2010, Mary Ann Liebert, Inc.
Subjects
CpG; Herceptin; Natural killer cells; Neoadjuvant immunotherapy; Radiosensitization
SDGs
Other Subjects
CpG oligodeoxynucleotide; epidermal growth factor receptor 2; RNA directed DNA polymerase; trastuzumab; antineoplastic agent; cyclopropane derivative; guanosine; monoclonal antibody; N2-cyclopropylamine-guanosine; trastuzumab; adjuvant chemotherapy; adolescent; animal experiment; animal model; article; cancer cell culture; cancer immunotherapy; cancer inhibition; cell activation; colon cancer; controlled study; female; human; human cell; immune response; in vitro study; in vivo study; mouse; natural killer cell; nonhuman; oncogene neu; priority journal; radiosensitivity; radiosensitization; spleen cell; adjuvant therapy; analogs and derivatives; animal; Bagg albino mouse; biosynthesis; Colonic Neoplasms; enzymology; immunology; immunotherapy; metabolism; natural killer cell; procedures; radiation dose; tumor cell line; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cell Line, Tumor; Colonic Neoplasms; Cyclopropanes; Guanosine; Humans; Immunotherapy; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Neoadjuvant Therapy; Radiation Tolerance; Receptor, ErbB-2
Type
journal article