title: Establishment of anti-mesothelioma monoclonal antibodies.
abstract: BACKGROUND
  Mesotheliomas are aggressive, therapy-resistant tumors that are predicted to increase in incidence at least until 2020. The prognosis of patients with mesothelioma is generally poor because they are typically diagnosed at a late stage and their tumors are resistant to current conventional therapies. For these reasons, improved diagnosis and therapy are urgently required. To address these issues, the aim of our research was to develop novel mesothelioma-specific monoclonal antibodies (mAbs) as diagnostic and therapeutic agents.
  
  
  METHODS
  To develop anti-mesothelioma mAbs useful for diagnosis and therapy, we repeatedly immunized a BALB/c mouse with viable mesothelioma cells, alternating between those from three mesothelioma cell lines. We hybridized the spleen cells from this immunized mouse with P3U1 myeloma cells. We then screened supernatants harvested from the hybridoma clones by assessing whether they bound to a mesothelioma cell line not used for immunization and altered its morphology. We designed this developmental strategy to reduce the risk of obtaining clonotypic mAbs against a single mesothelioma cell line.
  
  
  RESULTS
  Our newly generated mouse anti-human mAbs immunostained clinical samples of mesotheliomas. One of the newly generated mAbs did not react with any other tumor cell line tested. Two other mAbs significantly inhibited the proliferation of mesothelioma cells.
  
  
  CONCLUSIONS
  These newly generated anti-mesothelioma mAbs are potentially useful as diagnostic and therapeutic agents for mesothelioma. Moreover, our novel strategy for establishing antitumor mAbs may facilitate the development of new diagnostic and therapeutic techniques for mesotheliomas and other malignancies.
authors.affiliation: Department of Pathology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan.|Departments of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Mizutani
authors.affiliation: Departments of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Abe
authors.affiliation: Departments of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. matsuoka@juntendo.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Matsuoka
authors.affiliation: Departments of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kajino
authors.affiliation: Departments of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.|Department of Pathology, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji-shi, Tokyo, 193-0998, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Wakiya
authors.affiliation: Departments of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohtsuji
authors.affiliation: Therapy Development and Innovation for Immune Disorders and Cancers, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatano
authors.affiliation: Therapy Development and Innovation for Immune Disorders and Cancers, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
authors.affiliation: Departments of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000918:Antibody Specificity / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology; D008807:Mice, Inbred BALB C
chemical_list: D000911:Antibodies, Monoclonal
keywords: Diagnosis; Mesothelioma; Method; Monoclonal antibody; Therapy