Portal de Periódicos da CAPES

Antitumor Effect of Antibody against a SEREX-Defined Antigen (UOEH-LC-1) on Lung Cancer Xenotransplanted into Severe Combined Immunodeficiency Mice

2007; American Association for Cancer Research; Volume: 67; Issue: 17 Linguagem: Inglês

10.1158/0008-5472.can-06-3889

1538-7445

Makiko Mizukami, Takeshi Hanagiri, Manabu Yasuda, Koji Kuroda, Yoshiki Shigematsu, Tetsuro Baba, Takashi Fukuyama, Yoshika Nagata, Tetsuya So, Yoshinobu Ichiki, Masakazu Sugaya, Tomoko So, Mitsuhiro Takenoyama, Kenji Sugio, Kosei Yasumoto,

Glycosylation and Glycoproteins Research

Abstract 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. [Cancer Res 2007;67(17):8351–7]