A novel human monoclonal antibody derived from tumor-infiltrating lymphocytes in lung cancer inhibits cancer cell growth with morphological changes.
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.
Aoki
Masahiko
M
Department of Surgery and 3Research Park, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.
Saikawa
Yoshiro
Y
Hosokawa
Saiko
S
Fukuda
Kazumasa
K
Kumai
Koichiro
K
Kubota
Tetsuro
T
Yoshida
Masashi
M
Otani
Yoshihide
Y
Kitajima
Masaki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D048708:Cell Growth Processes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007116:Immunization, Passive / Q000379:methods; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal