A novel human monoclonal antibody derived from tumor-infiltrating lymphocytes in lung cancer inhibits cancer cell growth with morphological changes

Masahiko Aoki, Yoshiro Saikawa, Saiko Hosokawa, Kazumasa Fukuda, Koichiro Kumai, Tetsuro Kubota, Masashi Yoshida, Yoshihide Otani, Masaki Kitajima

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4 Citations (Scopus)

Abstract

Tumor-infiltrating lymphocytes (TIL) were isolated from surgically resected human samples using hybridoma techniques, and human monoclonal antibodies (HuMoAbs) were produced. Stable antibody-producing hybridoma cell lines were established and, on the basis of reactivity to human cancer cell lines, a clone of HuMoAb, named HoAKs-1, was selected. By confocal microscopy, we confirmed that HoAKs-1 showed specific and intense reactivity to the cell membrane of HLC-1 and PANC-1, wheareas the antibody did not show reactivity to human umbilical vein endothelial cells (HUVECs). Using xenografts formed from epithelial cancer cell lines in nude mice, we also demonstrated a broad spectrum of reactivity of the antibody in 6 out of 14 xenografts. In addition, using surgically resected clinical specimens from two patients with lung cancer, we showed that HoAKs-1 had specific reactivity to cancerous lesions but not to normal sites. In an in vitro experiment, HoAKs-1 induced morphological changes with neurite-like cytoplasmic processes in MKN-45, HLC-1 and PANC-1, whereas no morphological alterations were observed in HUVECs. Growth inhibition rates by HoAKs-1 were 63% in HLC-1 and 47% in MKN-45, while no growth inhibition occurred in normal HUVECs. We confirmed that HoAKs-1 recognized a 55 kDa protein by determining the molecular weight of the HoAKs-1 reacting protein. In conclusion, we successfully produced a novel HuMoAb, HoAKs-1, which reacted specifically to cancer cells and inhibited cell growth with morphological changes. HoAKs-1 may have the potential to be utilized as an anticancer agent, without causing any immunological reaction in humans.

Original languageEnglish
Pages (from-to)3791-3798
Number of pages8
JournalAnticancer research
Volume25
Issue number6 B
Publication statusPublished - 2005 Nov
Externally publishedYes

Keywords

  • Hybridoma
  • Lung cancer
  • Monoclonal antibody
  • Tumor-infiltrating B lymphocyte

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Aoki, M., Saikawa, Y., Hosokawa, S., Fukuda, K., Kumai, K., Kubota, T., Yoshida, M., Otani, Y., & Kitajima, M. (2005). A novel human monoclonal antibody derived from tumor-infiltrating lymphocytes in lung cancer inhibits cancer cell growth with morphological changes. Anticancer research, 25(6 B), 3791-3798.