Selection and analysis of anti-cancer antibodies for cancer therapy obtained from antibody phage library

Gene Kurosawa, Mariko Sumitomo, Yoshinori Ukai, Juvy Subere, Chiho Muramatsu, Keiko Eguchi, Miho Tanaka-Hashiba, Mai Sugiura, Misaki Ando, Noriko Sato, Miwa Morita, Kazuki Inaba, Satoko Morigaki, Akihiko Takasaki, Yasushi Akahori, Shuichi Miyakawa, Ichiro Uyama, Koutarou Maeda, Ryoichi Shiroki, Kiyotaka HoshinagaYoshikazu Mizoguchi, Yoshinobu Hattori, Atsushi Sugioka, Mototaka Sugiura, Yoshikazu Kurosawa

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The search for effective antibodies (Ab) for curable cancer immunotherapy has been a quest of many research groups in order to find an effective target that exists on the cancer cell surface. So far there have been no conclusive answers to shed light on the search. This study therefore aimed to bridge the gap of cancer therapy. Screening against 49 kinds of cell lines belonging to 11 kinds of solids cancers was performed. Isolation and characterization for approximately 4200 monoclonal antibodies (mAb) was also performed thereafter. Of those mAb 488 clones that turned out to bind to 29 tumor-associated antigens (TAA) were subjected to immunohistochemical (IHC) analyses. Selection of target antigens (Ag) and a potential antibody for cancer therapy was conducted prior to clinical examinations. In order to find predictably effective targets for therapeutic Ab against solid cancers, expression of the Ag on the surface of cancer and normal cells was extensively examined by IHC analyses using fresh cancer specimens resected from patients. In this study, the tendencies of all staining patterns and distribution of the Ab are reported. While all of the TAA appeared to be involved in tumorigenesis, their expression was not restricted to some specific tumor types but rather randomly distributed among various cancers. Some kinds of Ab including anti-epidermal growth factor receptor (EGFR) and anti-human epidermal growth factor receptor 2 (HER2) indicated the frequency of expression in normal cells was generally low. We concluded that identification of 488 mAb and the accumulated results of IHC analyses in this study could be the key for further therapeutic Ab against cancers. The targets that showed cancer-specific expression are expected to be better for therapeutic Ab than the other Ab. Moreover, further investigation into the growth of cancer cell lines using full human IgG form of Ab shows available efficacy in specific cases.

Original languageEnglish
Pages (from-to)175-181
Number of pages7
JournalCancer science
Volume102
Issue number1
DOIs
Publication statusPublished - 01-2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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