Classification of 27 Tumor-Associated Antigens by Histochemical Analysis of 36 Freshly Resected Lung Cancer Tissues.
In previous studies, we identified 29 tumor-associated antigens (TAAs) and isolated 488 human monoclonal antibodies (mAbs) that specifically bind to one of the 29 TAAs. In the present study, we performed histochemical analysis of 36 freshly resected lung cancer tissues by using 60 mAbs against 27 TAAs. Comparison of the staining patterns of tumor cells, bronchial epithelial cells, and normal pulmonary alveolus cells and interalveolar septum allowed us to determine the type and location of cells that express target molecules, as well as the degree of expression. The patterns were classified into 7 categories. While multiple Abs were used against certain TAAs, the differences observed among them should be derived from differences in the binding activity and/or the epitope. Thus, such data indicate the versatility of respective clones as anti-cancer drugs. Although the information obtained was limited to the lung and bronchial tube, bronchial epithelial cells represent normal growing cells, and therefore, the data are informative. The results indicate that 9 of the 27 TAAs are suitable targets for therapeutic Abs. These 9 Ags include EGFR, HER2, TfR, and integrin α6β4. Based on our findings, a pharmaceutical company has started to develop anti-cancer drugs by using Abs to TfR and integrin α6β4. HGFR, PTP-LAR, CD147, CDCP1, and integrin αvβ3 are also appropriate targets for therapeutic purposes.
Division of Antibody Project, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake 470-1192, Japan. gene@fujita-hu.ac.jp.
Gene
G
Kurosawa
Internal Medicine, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan. msugiura@fujita-hu.ac.jp.
Mototaka
M
Sugiura
Division of Thoracic and Cardiovascular Surgery, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan. y-hattori@daidohp.or.jp.|Department of Surgery, Social Medical Corporation Kojunkai Daido Hospital, Nagoya 457-8511, Japan. y-hattori@daidohp.or.jp.
Yoshinobu
Y
Hattori
Department of Toxicology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8603, Japan. htsuda@phar.nagoya-cu.ac.jp.
Hiroyuki
H
Tsuda
Division of Antibody Project, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake 470-1192, Japan. kurosawa@fujita-hu.ac.jp.
Yoshikazu
Y
Kurosawa
D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000145:classification* / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000601:surgery; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D039161:Integrin alpha6beta4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000601:surgery; D058990:Molecular Targeted Therapy / Q000379:methods*; D019151:Peptide Library; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000939:Epitopes; D066246:ErbB Receptors; D039161:Integrin alpha6beta4; D019151:Peptide Library; D018719:Erb-b2 Receptor Tyrosine Kinases; D011990:Receptors, Transferrin; C512478:EGFR protein, human; C508053:ERBB2 protein, human
cancer-associated antigens; combination therapy; histochemical analysis; phage-display antibody library; therapeutic antibody