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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Jan;84(1):75–82. doi: 10.1111/j.1349-7006.1993.tb02787.x

A Cancer‐reactive Human Monoclonal Antibody Derived from a Colonic Cancer Patient Treated with Local Immunotherapy

Toshio Yagyu 1, Takushi Monden 1, Masashi Baba 1, Yasuhiro Tamaki 1, Tsutomu Takeda 1, Tetsuro Kobayashi 1, Takashi Shimano 1, Yoshiyuki Tsuji 2, Hirohisa Matsushita 3, Hisao Osawa 3, Hiroki Murakami 4, Takesada Mori 1
PMCID: PMC5919026  PMID: 8449830

Abstract

A human monoclonal antibody, YJ‐37 (IgM) was generated through the fusion of human B lymphoblastoid cell line HO‐323 with the regional lymph node lymphocytes from a colonic cancer patient who was treated with a local immunotherapy. This antibody was purified and conjugated with biotin, after which direct immunohistochemical staining was performed. The results revealed that YJ‐37 selectively reacted with colonic cancer (7/19), gastric cancer (3/6), endometrial cancer (1/2) and colonic adenoma (7/13), but not with normal epithelia. Membrane immunofluorescence and FACS analysis also showed that YJ‐37 bound to tumor cell surfaces. Furthermore, the chemical structure of the antigen defined by YJ‐37 was analyzed by means of thin‐layer chromatography immunostaining and ELISA. The results indicated that YJ‐37 reacted with sialylated lacto‐series carbohydrate chains, which have been reported to accumulate in cancer cells.

Keywords: Human monoclonal antibody, Local immunotherapy, Colon cancer, Tumor cell surface, Sialylated lacto‐series carbohydrate antigen

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REFERENCES

  • 1. ) Katano , M. , Ming , J. and Irie , R. F.Human monoclonal antibody to ganglioside GD2‐inhibited human melanoma xenograft . Eur. J. Cancer Clin. Oncol. , 20 , 1053 – 1059 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Irie , R. F. and Morton , D. L.Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2 . Proc. Natl. Acad. Sci. USA , 83 , 8694 – 8698 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) Irie , R. F. , Takasumi , M. and Morton , D. L.Human monoclonal antibody to ganglioside GM2 for melanoma treatment . Lancet , i , 786 – 787 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Cote , R. J. , Morrissey , D. M. , Houghton , A. N. , Thomson , T. M. , Daly , M. E. , Oettgen , H. F. and Old , L. J.Specificity analysis of human monoclonal antibodies reactive with cell surface and intracellular antigens . Proc. Natl. Acad. Sci. USA , 83 , 2959 – 2963 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Formenti , S. C. , Mitchell , M. S. , Taylor , C. R. , Lipkin , M. , Jernstrom , P. H. and Kan‐Mitchell , J.Reactivity of a human monoclonal antibody against carcinomas and other lesions of the colon . Cancer Immunol. Immunother. , 28 , 296 – 300 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Borup‐Christensen , P. , Erb , K. , Jensenius , J. C. , Nielsen , B. and Svehag , S. E.Human‐human hybridomas for the study of anti‐tumor immune response in patients with colorectal cancer . Int. J. Cancer , 37 , 683 – 688 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Starling , J. J. , Cote , R. J. , Marder , P. , Borowitz , M. J. and Johnson , D. A.Tissue distribution and cellular location of the antigens recognized by human monoclonal antibodies 16.88 and 28A32 . Cancer Res. , 48 , 7273 – 7278 ( 1988. ). [PubMed] [Google Scholar]
  • 8. ) Haspel , M. V. , McCabe , R. P. , Pomato , N. , Janesch , N. J. , Knowlton , J. V. , Perters , L. C. , Hoover , H. C. , Jr. and Hanna , M. G. , Jr.Generation of tumor cell‐reactive human monoclonal antibodies using peripheral blood lymphocytes from actively immunized colorectal carcinoma patients . Cancer Res. , 45 , 3951 – 3961 ( 1985. ). [PubMed] [Google Scholar]
  • 9. ) Koyama , K. , Akiyama , K. , Kawahara , H. , Egashira , A. and Murakami , H.Alloimmunization with cultured human stomach cancer cell lines and the establishment of human‐human hybridomas producing monoclonal antibodies . Jpn. J. Cancer Res. , 81 , 967 – 970 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. ) Yagyu , T. , Monden , T. , Tamaki , Y. , Morimoto , H. , Takeda , T. , Kobayashi , T. , Shimano , T. , Murakami , H. and Mori , T.Use of a local immunotherapy as an adjunctive tool for the generation of human monoclonal antibodies from regional lymph nodes of colonic cancer patients . Jpn. J. Cancer Res. , 83 , 20 – 23 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. ) Monden , T. , Morimoto , H. , Shimano , T. , Yagyu , T. , Murotani , M. , Nagaoka , H. , Kawasaki , Y. , Kobayashi , T. and Mori , T.Use of fibrinogen to enhance the antitumor effect of OK‐432, A new approach to immunotherapy for colorectal carcinoma . Cancer , 69 , 636 – 642 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Ohashi , H. , Hashizume , S. , Murakami , H. , Aihara , K. , Shinohara , K. and Omura , H.HO‐323, a human B‐lymphoblastoid cell line useful for making human‐human hybridomas . Cell Biol. Int. Rep. , 10 , 77 – 83 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Tamaki , Y. , Kobayashi , T. , Higashiyama , M. , Shimano , T. , Mori , T. and Murakami , H.A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient . Hybridoma , 8 , 293 – 302 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Haruna , N. , Monden , T. , Morinoto , H. , Murotani , M. , Yagyu , T. , Nagooka , H. , Shimano , T. and Mori , T.The use of rapid microwave fixation technique for immunocytochemical demonstration of tumor necrosis factor, interleukin‐lα, and interleukin‐1β in activated human peripheral mononuclear cells . Acta Histochem. Cytochem. , 23 , 563 – 572 ( 1990. ). [Google Scholar]
  • 15. ) Bonnard , C. , Papermaster , D. and Kraehenbuhl , J. P.The streptavidin‐biotin bridge technique: application in light and electron microscope immunocytochemistry . In “ Immunolabelling for Electron Microscopy ,” ed. Polak J. M. and Varndell I. M. , pp. 95 – 111 ( 1984. ). Elsevier Scientific Publishers; , Amsterdam . [Google Scholar]
  • 16. ) Tsuji , Y. , Clausen , H. , Nudelman , E. , Kaizu , T. , Hakomori , S. and Isojima , S.Human sperm carbohydrate antigens defined by an antisperm human monoclonal antibody derived from an infertile woman bearing antisperm antibodies in her serum . J. Exp. Med. , 168 , 343 – 356 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Kannagi , R. , Leverry , S. B. , Ishigami , F. , Hakomori , S. , Shevinsky , L. H. , Knowless , B. B. and Solter , D.New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen, stage‐specific embryonic antigen 3 . J. Biol. Chem. , 258 , 8934 – 8942 ( 1983. ). [PubMed] [Google Scholar]
  • 18. ) Kannagi , R. , Nudelman , E. , Leverry , S. B. and Hakomori , S.A series of human erythrocyte glycosphingolipids reacting to the monoclonal antibody directed to a developmentally regulated antigen, SSEA‐1 . J. Biol. Chem. , 257 , 14865 – 14874 ( 1982. ). [PubMed] [Google Scholar]
  • 19. ) Magani , J. L. , Smith , D. F. and Ginsburg , V.Detection of gangliosides that bind cholera toxin: direct binding of 125I‐labeled toxin to thin‐layer chromatograms . Anal. Biochem. , 109 , 399 – 402 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Baba , M. , Kobayashi , T. , Tamaki , Y. , Mishima , H. , Yagyu , T. , Morimoto , H. , Monden , T. , Shimano , T. , Tsuji , Y. , Murakami , H. and Mori , T.A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient reactive to a sulfated glycolipid . Hybridoma , 11 , 107 – 119 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Hakomori , S.Aberrant glycosylation in tumors and tumor‐associated carbohydrate antigens . Adv. Cancer Res. , 52 , 257 – 331 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Phillips , M. L. , Nudelman , E. , Gaeta , F. C. A. , Perez , M. , Singhal , A. K. , Hakomori , S. and Paulson , J.ELAM‐1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl‐Lex . Science , 250 , 1130 – 1132 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Walz , G. , Aruffo , A. , Kolanus , W. , Bevilacqua , M. and Seed , B.Recognition by ELAM‐1 of the sialyl‐Lex determinant on myeloid and tumor cells . Science , 250 , 1132 – 1135 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Nilsson , O. , Mansson , J. E. , Lindoholm , L. , Holmgren , J. and Svennerholm , L.Sialosyllactotetraosylceramide, a novel ganglioside antigen detected in human carcinomas by a monoclonal antibody . FEBS Lett. , 182 , 398 – 402 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Retting , W. J. , Cordon‐Cardo , C. , Ng , J. S. C. , Oettgen , H. F. , Old , L. J. and Lloyd , K. O.High‐molecular‐weight glycoproteins of human teratocarcinoma defined by monoclonal antibodies to carbohydrate determinants . Cancer Res. , 45 , 815 – 821 ( 1985. ). [PubMed] [Google Scholar]
  • 26. ) Fukuda , M. N. , Bothner , B. , Lloyd , K. O. , Retting , W. J. , Tiller , P. R. and Dell , A.Structures of glycosphingolipids isolated from human embryonal carcinoma cells . J. Biol. Chem. , 261 , 5145 – 5153 ( 1986. ). [PubMed] [Google Scholar]
  • 27. ) Nagaoka , H. , Monden , T. , Sakita , I. , Katsumoto , Y. , Wakasugi , T. , Kawasaki , Y. , Takeda , T. , Yagyu , T. , Morimoto , H. , Kobayashi , T. , Shimano , T. and Mori , T.Establishment of cytotoxic CD4+ T cell clones from regional lymph nodes of colonic cancer patients treated by local immunotherapy . Biotherapy , in press . [DOI] [PubMed] [Google Scholar]

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