Antitumor effect of antibody against a SEREX-defined antigen (UOEH-LC-1) on lung cancer xenotransplanted into severe combined immunodeficiency mice.
We previously reported the humoral immune response of tumor-infiltrating B lymphocytes in a lung cancer patient and 22 genes coding tumor-associated antigens identified using the serological identification of antigens by recombinant expression cloning method. In this study, we investigated one of these genes, designated University of Occupational and Environmental Health-Lung cancer antigen-1 (UOEH-LC-1), which has an extracellular domain. Quantitative reverse transcription-PCR revealed that UOEH-LC-1 was expressed ubiquitously in the normal tissues tested. However, it was overexpressed in 5 of 11 (45.5%) lung cancer cell lines and also in 9 of 15 (60%) lung cancer tissues compared with the paired normal lung tissues. A sequence analysis revealed that UOEH-LC-1 has a transmembrane domain. Flow cytometry analysis using a polyclonal antibody against UOEH-LC-1 revealed positive staining on lung cancer cell lines that were positive for expression of mRNA of UOEH-LC-1. Phage plaque assay showed the specific reactivity of anti-UOEH-LC-1 antibody against UOEH-LC-1 protein derived from the antigen encoding phage. By immunohistochemical staining with the anti-UOEH-LC-1 antibody, 7 of 28 (25.0%) lung cancer specimens showed positive staining on the cell surface. The administration of anti-UOEH-LC-1 antibody inhibited the growth of the UOEH-LC-1-positive tumors that were xenotransplanted into severe combined immunodeficiency mice. Complement-dependent cytotoxicity was one of the mechanisms to suppress the tumor growth. These results suggest that the antibody against UOEH-LC-1 therefore seems to have a promising therapeutic potential as a treatment for lung cancer.
Mizukami
Makiko
M
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Hanagiri
Takeshi
T
Yasuda
Manabu
M
Kuroda
Koji
K
Shigematsu
Yoshiki
Y
Baba
Tetsuro
T
Fukuyama
Takashi
T
Nagata
Yoshika
Y
So
Tetsuya
T
Ichiki
Yoshinobu
Y
Sugaya
Masakazu
M
So
Tomoko
T
Takenoyama
Mitsuhiro
M
Sugio
Kenji
K
Yasumoto
Kosei
K
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays