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Effectiveness of vitamin A acetate for enhancing the production of lung cancer specific monoclonal antibodies

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Abstract

The antibody productivity of the human–human hybridoma cell line AE6, which produces the lung cancer specific human monoclonal antibody AE6F4, was enhanced fourfold upon stimulation with 1 μg/ml of vitamin A acetate for one day. The enhancement lasted for about two weeks, and could be repeated by another stimulation with vitamin A acetate. The enhancing effect of vitamin A acetate was influenced by the cell density. Enhancement was clearly observed when the cell density was under 106 cells/ml. However, when the cell density was over 107 cells/ml, enhancement was observed weakly or not at all. Although the enhancing effect of vitamin A acetate is not unique to AE6 cells, not all human–human hybridoma cell lines show increased productivity upon VA acetate stimulation. This study suggests that the response to vitamin A acetate may be related to the properties of a particular fusion partner which the hybridoma cell inherits. The efficacy of vitamin A acetate for production of human monoclonal antibodies using human–human hybridomas is discussed.

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References

  • Aotsuka Y and Naito M (1991) Enhancing effects of retinoic acid on monoclonal antibody production of human-human hybridomas. Cell Immunol 133: 498–505.

    Article  CAS  Google Scholar 

  • Ballow M, Wang W and Xiang S (1996) Modulation of B-cell immunoglobulin synthesis by retinoic acid. Clin Immunol Immunopathol 80: 73–81.

    Article  Google Scholar 

  • Blomhoff HK, Smeland EB, Erikstein B, Rasmussen AM, Skrede B, Skjonsberg C and Blomhoff R (1992) Vitamin A is a key regulator for cell growth, cytokine production, and differentiation in normal B cells. J Biol Chem 267: 23988–23992.

    CAS  Google Scholar 

  • Chaiwun B, Saad A, Chatterjee SJ, Taylor CR, Beattie EJ and Cote RJ (1996) Advances in the pathologic staging of lung cancer: detection of regional and systemic occult metastases. Pathology Phila 4: 155–168.

    CAS  Google Scholar 

  • Chen AC and Gudas LJ (1996) An analysis of retinoic acid-induced gene expression and metabolism in AB1 embryonic stem cells. J Biol Chem 271: 14971–14980.

    Article  CAS  Google Scholar 

  • Desai D, Michalak M, Singh NK and Niles RM (1996) Inhibition of retinoic acid receptor function and retinoic acid-regulated gene expression in mouse melanoma cells by calreticulin. J Biol Chem 271: 15153–15159.

    Article  CAS  Google Scholar 

  • Eichele G (1989) Retinoids and vertebrate limb pattern formation. Trends Genet 5: 246–251.

    Article  CAS  Google Scholar 

  • Garbe A, Buck J and Hammerling U (1992) Retinoids are important cofactors in T cell activation. J Exp Med 176: 109–117.

    Article  CAS  Google Scholar 

  • Hespanhol V, Queiroga H, Magalhaes A, Santos AR, Coelho M and Marques A (1995) Survival predictiors in advanced non-small cell lung cancer. Lung cancer 13: 253–267.

    Article  CAS  Google Scholar 

  • Inoue Y, López LB, Kawamoto S, Arita N, Teruya K, Seki K, Shoji M, Kamei M, Hashizume S, Shiozawa Y, Tachibana H, Ohashi H, Yasumoto K, Nagashima A, Nakahashi H, Suzuki T, Imai T, Nomoto K, Takenouchi M, Katakura Y and Shirahata S (1996a) Production of recombinant human monoclonal antibody using ras-amplified BHK-21 cells in a protein-free medium. Biosci Biotech Biochem 60: 811–817.

    Article  CAS  Google Scholar 

  • Inoue Y, Kawamoto S, Seki K, Teruya K, Mochizuki K, Kato M, Hashizume S, Yasumoto K, Nagashima A, Nakahashi H, Suzuki T, Imai T, Nomoto K and Shirahata S (1996b) Production of a recombinant human monoclonal antibody using a novel hollow fiber bioreactor system. J Ferment Bioeng 81: 466–469.

    Article  CAS  Google Scholar 

  • Kawahara H, Shirahata S, Tachibana H and Murakami H (1992) In vitro immunization of human lymphocytes with human lung cancer cell line A549. Hum Antibod Hybridomas 3: 8–13.

    CAS  Google Scholar 

  • Kontani K, Nishina H, Ohoka Y, Takahashi K and Katada T (1993) NAD glycohydrolase specifically induced by retinoic acid in human leukemic HL-60 cells. Identification of the NAD glycohydrolase as leukocyte cell surface antigen CD38. J Biol Chem 268: 16895–16898.

    CAS  Google Scholar 

  • Minucci S, Leid M, Toyama R, Saint Jeannet JP, Peterson VJ, Horn V, Ishmael JE, Bhattacharyya N, Dey A, Dawid IB and Ozato K (1997) Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression. Mol Cell Biol 17: 644–655.

    CAS  Google Scholar 

  • Murakami H, Hashizume S, Ohashi H, Shinohara K, Yasumoto K, Nomoto K and Omura H (1985) Human-human hybridomas secreting antibodies specific to human lung carcinoma. In Vitro Cell Dev Biol 21: 593–596.

    CAS  Google Scholar 

  • Nakayama H, Tsiboi M, Kaneko M and Naruke T (1996) Early lung cancer. Nippon Rinsho 54: 1359–1365.

    CAS  Google Scholar 

  • Pierce R, Irving L and Barter C (1996) Update on lung cancer. Aust Fam Physician 25: 177–179, 181, 184–188.

    CAS  Google Scholar 

  • Pomponi F, Cariati R, Zancai P, De Paoli P, Rizzo S, Tedeschi RM, Pivetta B, De Vita S, Boiocchi M and Dolcetti R (1996) Retinoids irreversibly inhibit in vitro growth of Epstein-Barr virus-immortalized B lymphocytes. Blood 88: 3147–3159.

    CAS  Google Scholar 

  • Rius C and Aller P (1992) Vimentin expression as a late event in the in vitro differentiation of human promonocytic cells. J Cell Sci 101: 395–401.

    CAS  Google Scholar 

  • 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 and Murakami H (1994a) Specific reactivity of human antibody AE6F4 against cancer cells in tissues and sputa from lung cancer patients. Hum Antibod Hybridomas 5: 116–122.

    CAS  Google Scholar 

  • Shoji M, Kawamoto S, Setoguchi Y, Mochizuki K, Honjoh T, Kato M, Hashizume S, Hanagiri T, Yoshimatsu T, Nakanishi K, Yasumoto K, Nagashima A, Nakahashi H, Suzuki T, Imai T, Nomoto K and Murakami H. (1994b) The 14–3–3 protein as the antigen for lung cancer-associated human monoclonal antibody AE6F4. Hum Antibod Hybridomas 5: 123–130.

    CAS  Google Scholar 

  • Suzuki E and Ollis DF (1990) Enhanced antibody production at slow growth rate: experimental demonstration and a simple structural model. Biotechnol Prog 6: 231–236.

    Article  CAS  Google Scholar 

  • Takahashi K, Tereda S, Ueda H, Makishima F and Suzuki E (1994) Growth rate suppression of cultured mammlian cells enhances protein productivities. Cytotechnology 15: 57–64.

    Article  CAS  Google Scholar 

  • Vu Dac N, Schoonjans K, Kosykh V, Dallongeville J, Heyman RA, Staels B and Auwerx J (1996) Retinoids increase human apolipoprotein A-II expression through activation of the retinoid X receptor but not the retinoic acid receptor. Mol Cell Biol 16: 3350–3360.

    CAS  Google Scholar 

  • Wang W, Napoli JL and Ballow M (1993) The effects of retinol on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells. Clin Exp Immunol 92: 164–168.

    Article  CAS  Google Scholar 

  • Yano T, Teruya K, Shirahata S, Watanabe J, Osada K, Tachibana H, Ohashi H, Kim EH and Murakami H (1994) Ras oncogene enhances the production of a recombinant protein regulated by the cytomegalovirus promoter in BHK-21 cells. Cytotechnology 16: 167–178.

    Article  CAS  Google Scholar 

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Inoue, Y., Fujisawa, M., Kawamoto, S. et al. Effectiveness of vitamin A acetate for enhancing the production of lung cancer specific monoclonal antibodies. Cytotechnology 31, 77–83 (1999). https://doi.org/10.1023/A:1008016020785

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  • DOI: https://doi.org/10.1023/A:1008016020785

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