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. 2001 Jul;36(1-3):171–177. doi: 10.1023/A:1014049205434

Establishment of hybridomas producing cancer specific human antibodies from B cell line derived from PBL of a patient with adult T cell leukemia

Takeshi Kawahara 1, Akira Ichikawa 1, Yoshinori Katakura 1, Kiichiro Teruya 1, Takahisa Yoshida 2, Masahiro Kikuchi 3, Masanori Kamei 4, Shuichi Hashizume 4, Sanetaka Shirahata 5,✉
PMCID: PMC3449666  PMID: 19003328

Abstract

Adult T cell leukemia (ATL) is a malignant disease characterized by tumorous proliferation of CD4+ T cells infected with retrovirus human T cell leukemia virus Type-I (HTLV-I) and concurs with an autoimmune disease and cancer due to attenuated immune response. In this study, we established ATL patient derived B-cell line TM-1 producing cancer-specific IgM antibodies, and further characterized its antigen specificity by establishing hybridomas fused with human-mouse origin hetero-myeloma cell line RF-S1. We established three hybridoma cell lines termed 2E12, 3E9, and 3E10, which continuously secreted human IgM antibodies. Immunohistochemical staining of formalin-fixed tissue section using antibodies secreted from these hybridomas showed that these antibodies specifically recognized tumor sites of human colon adenocarcinomas. Antibody produced from hybridoma 3E9 bound to some of leukemic cell lines, but not to normal human PBL, which was evidenced by the flow cytometric analysis, indicating that antibody produced from 3E9 recognizes cell surface antigen specifically expressed in the leukemic cells.

Keywords: adult T-cell leukemia, cancer, human monoclonal antibody, hybridomas

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References

  1. Aihara K, Yamada K, Murakami H, Nomura Y, Omura H. Production of human-human hybridomas secreting monoclonal antibodies reactive to breast cancer cell lines. In Vitro Cell Develop Biol. 1988;24:959–962. doi: 10.1007/BF02623911. [DOI] [PubMed] [Google Scholar]
  2. Hashizume S, Sato S, Matsuyama M, Tamaki S, Hanada K, Murakami H, Yasumoto K, Nomoto K, Nakano K, Kusakabe K. Accumulation of 125I-labelled human monoclonal antibody (HB4C5), specific to lung cancer, into transplanted human lung cancer in nude mouse. In: Murakami H, editor. Trends in Animal Cell Culture Technology. Kodansha: VCH; 1990. pp. 167–172. [Google Scholar]
  3. Imajo K, Shinagawa K, Tada S, Tsubota T, Kimura I. Detection of the pX gene of human T-lymphotropic virus type I in respiratory diseases with diffuse interstitial pulmonary shadows and lung cancer. Acta Medica Okayama. 1993;47:363–368. doi: 10.18926/AMO/31560. [DOI] [PubMed] [Google Scholar]
  4. Kawahara H, Shirahata S, Tachibana H, Murakami H. In vitro immunization of human lymphocytes with human lung cancer cell line A549. Hum Antibodies Hybridomas. 1992;3:8–13. [PubMed] [Google Scholar]
  5. Kjeldsen B, Rasmussen BB, Rose C, Zeuthen J. Humanhuman hybridomas and human monoclonal antibodies obtained by fusion of lymph node lymphocytes from breast cancer patients. Cancer Res. 1988;48:3208–3214. [PubMed] [Google Scholar]
  6. Matsuzaki H, Asou N, Kawaguchi Y, Hata H, Yoshinaga T, Kinuwaki E, Ishii T, Yamaguchi K, Takatsuki K. Human T-cell leukemia virus type 1 associated with small cell lung cancer. Cancer. 1990;66:1763–1768. doi: 10.1002/1097-0142(19901015)66:8<1763::AID-CNCR2820660821>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  7. Matsuzaki H, Hata H, Asou N, Yoshida M, Matsuno F, Takeya M, Yamaguchi K, Sanada I, Takatsuki K. Human T-cell leukemia virus-1-positive cell line established from a patient with small cell lung cancer. Jap J Cancer Res. 1992;83:450–457. doi: 10.1111/j.1349-7006.1992.tb01949.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Morishita R, Koura S, Tara M, Tokunaga M, Matsumoto T. Adult T-cell leukemia associate with cancer. Nippon Hifuka Gakkai Zasshi, Japanese J of Dermatology. 1989;99:37–43. [PubMed] [Google Scholar]
  9. Murata K, Miyoshi E, Kameyama M, Ishikawa O, Kabuto T, Sasaki Y, Hiratsuka M, Ohigashi H, Taniguchi N, Imaoka S. Expression of N-acetyl glucose aminyl transferase V (GnT-V) induces sialyl lewis X (sLex) antigen in human colorectal cancer: (RF2) Dis Colon Rectum. 2001;44:A2–A4. [Google Scholar]
  10. Nakamori S, Ota DM, Cleary KR, Shirotani K, Irimura T. MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology. 1994;106:353–361. doi: 10.1016/0016-5085(94)90592-4. [DOI] [PubMed] [Google Scholar]
  11. Nishimura E, Mochizuki K, Kato M, Hashizume S, Haruta H, Shirahata S, Suzuki T, Nomoto K, Kanaya K, Kusakabe K. Recombinant light chain of human monoclonal antibody HB4C5 as a potentially useful lung cancer-targeting vehicle. Hum Antibodies. 1999;9:111–124. [PubMed] [Google Scholar]
  12. Saijo S, Kotani M, Habu K, Ishitsuka C, Yamamoto H, Sekiguchi T, Iwakura Y. Bone marrow-derived cells are responsible for the development of autoimmune arthritis in human T cell leukemia virus type I-transgenic mice and those of normal mice can suppress the disease. J Immunol. 1999;163:5700–5707. [PubMed] [Google Scholar]
  13. Shoji M, Kawamoto S, Sato S, Kamei M, Kato M, Hashizume S, Seki K, Yasumoto K, Nagashima A, Nakahashi H, Suzuki T, Imai T, Nomoto K, Murakami H. Specific reactivity of human monoclonal antibody AE6F4 against cancer cells in tissues and sputa from lung cancer patients. Hum Antibodies and Hybridomas. 1994;5:116–122. [PubMed] [Google Scholar]
  14. Shoji M, Kawamoto S, Seki K, Teruya K, Setoguchi Y, Mochizuki K. K. M. H. S. H. T. Y. T. N. K., Yasumoto K, Nagashima A, Nakahashi H, Suzuki T, Imai T, Shirahata S, Nomoto K, Murakami H. Lung cancer-reacting human recombinant antibody AE6F4: Potential usefulness in the sputum cytodiagnosis. Hum Antibodies Hybridomas. 1996;7:27–36. [PubMed] [Google Scholar]
  15. Sugata T. Analysis of infiltrating T cells in the affected autoimmune lesions of HTLV-1 transgenic rats. Hokkaido Igaku Zasshi, Hokkaido J Med Sci. 2001;76:35–47. [PubMed] [Google Scholar]
  16. Takahashi T, Makiguchi Y, Hinoda Y, Kakiuchi H, Nakagawa N, Imai K, Yachi A. Expression of MUC1 onmyeloma cells and induction of HLA-unrestricted CTL against MUC1 from a multiple myeloma patient. J Immunol. 1994;153:2102–2109. [PubMed] [Google Scholar]
  17. Tamura K. Clinical classification of adult T-cell leukemia and its complications. Rinsho Byori, Jap J Clinical Pathology. 1996;44:19–23. [PubMed] [Google Scholar]
  18. Tsukazaki K, Kuroda K, Mochizuki K, Kubushiro K, Fukuchi T, Kato M, Hashizume S, Nozawa S. A human monoclonal antibody to carbohydrate moiety of carcinoembryonic antigen. Human Antibodies and Hybridomas. 1995;6:145–152. [PubMed] [Google Scholar]
  19. Tsukasaki K, Maeda T, Arimura K, Taguchi J, Fukushima T, Miyazaki Y, Moriuchi Y, Kuriyama K, Yamada Y, Tomonaga M. Poor outcome of autologous stem cell transplantation for adult T cell leukemiya/lympohoma: A case report and review of the literature. Bone Marrow Transplantation. 1999;23:87–89. doi: 10.1038/sj.bmt.1701533. [DOI] [PubMed] [Google Scholar]
  20. Zucker-Franklin D. Non-HIV retroviral association with rheumatic disease. Current Rheumatology Reports. 2000;2:156–162. doi: 10.1007/s11926-000-0056-0. [DOI] [PubMed] [Google Scholar]

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