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Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1993 May;37(3):143–149. doi: 10.1007/BF01525427

A human/mouse chimeric monoclonal antibody against CA125 for radioimmunoimaging of ovarian cancer

Hisataka Kobavashi 1,, Harumi Sakahara 1, Tsuneo Saga 1, Makoto Hosono 1, Makoto Shirato 1, Hidetoshi Kanda 2, Kaichiro Ishibashi 2, Takeshi Watanabe 3, Keigo Endo 4, Isamu Ishiwata 5, Junji Konishi 1
PMCID: PMC11038746  PMID: 7687520

Abstract

Murine monoclonal antibody 196-14 recognizes the ovarian-cancer-associated antigen CA 125, but the epitope it recognizes is different from that of monoclonal antibody OC125. We developed a human/mouse chimeric 196-14 using the variable regions of the murine 196-14 and human heavy-chain (γl) and light-chain (κ) constant regions. Cell binding and competitive inhibition assays using chimeric 196-14 labeled with125I,111In or99mTc demonstrated that the in vitro immunoreactivity of the chimeric antibody was identical to that of the parental murine monoclonal antibody. However, in mice bearing human ovarian cancer xenografts, the clearance from blood was faster and absolute levels of accumulation in the tumor were lower for the125I-labeled or99mTc-labeled chimeric antibody than for the murine antibody labeled with the corresponding radionuclides. The tumor-to-blood radioactivity ratio was not significantly different between the chimeric antibody and the murine antibody, regardless of the radionuclide used for labeling. Chimeric antibody 196-14 labeled with131I,111In or99mTc is promising for the radioimmunoimaging of ovarian cancer.

Key words: Monoclonal antibody, Immunodetection, CA125, Ovarian cancer

References

  • 1.Abdel-Nabi HH, Schwartz AN, Higano CS, Wechter DG, Unger MW. Colorectal carcinoma: detection with indium-111 anticarcinoembryonic-antigen monoclonal antibody ZCE-025. Radiology. 1987;164:617. doi: 10.1148/radiology.164.3.3303117. [DOI] [PubMed] [Google Scholar]
  • 2.Bast RC, Jr, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68:1331. doi: 10.1172/JCI110380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Berzen G, Mayr AC, Langer M, Becker R, Cordes M, Zwicker C, Koppenhagen K, Felix R. Radioimmunoscintigraphy of ovarian cancer with 131-iodine labeled OC-125 antibody fragments. Eur J Nucl Med. 1989;15:42. doi: 10.1007/BF00253598. [DOI] [PubMed] [Google Scholar]
  • 4.Boulianne GL, Hozumi N, Shulman MJ. Production of functional chimeric mouse/human antibody. Nature. 1984;312:643. doi: 10.1038/312643a0. [DOI] [PubMed] [Google Scholar]
  • 5.Brown BA, Davis GL, Saltzgaber-Mullaer J, Simon P, Ho M-K, Shaw PS, Stone BA, Sands H, Moore GP. Tumor-specific genetically engineered murine/human chimeric monoclonal antibody. Cancer Res. 1987;47:3577. [PubMed] [Google Scholar]
  • 6.Carrasquillo JA, Mulshine JL, Bunn PA, Jr, Reynolds JC, Foon KA, Schroff RW, Perentesis P, Steis RG, Keenan AM, Horowitz M, Larson SM. Indium-111-T101 monoclonal antibody is superior to iodine-131-T101 in imaging of cutaneous T-cell lymphoma. J Nucl Med. 1987;28:281. [PubMed] [Google Scholar]
  • 7.Chatal JF, Fumoleau P, Saccavini JC, Thedrez P, Curtet C, Bianco-Arco A, Chetanneau A, Peltier P, Kremer M. Immunoscintigraphy of recurrences of gynecologic carcinomas. J Nucl Med. 1987;28:1807. [PubMed] [Google Scholar]
  • 8.Davis HM, Zurawski VR, Jr, Bast RC, Jr, Klug TL. Characterization of the CA 125 antigen associated with human epitherial ovarian carcinomas. Cancer Res. 1986;46:6143. [PubMed] [Google Scholar]
  • 9.Dutin JP, Peltier P, Chatal JF. Bayesian analysis of the utility of In-111 OC 125 immunoscintigraphy (IS) in diagnosing ovarian cancer (abstract) J Nucl Med. 1991;32:941. [Google Scholar]
  • 10.Hamilton TC, Young RC, McKoy WM, Grotzinger KR, Green JA, Chu EW, Whang-Peng J, Rogan AM, Green WR, Ozols RF. Characterization of a human ovarian carcinoma cell line (NIH: OVCAR3) with androgen and estrogen receptors. Cancer Res. 1983;43:5379. [PubMed] [Google Scholar]
  • 11.Heal A, Tyson I, Robb S, Docs J, Courey M. Erroneous CA-125 values due to HAMA in serum of patients treated with mouse MoAbs (abstract) J Nucl Med. 1990;31:715. [Google Scholar]
  • 12.Hirano T, Tomiyoshi K, Watanabe N, Tateno M, Oriuchi N, Inoue T, Endo K. Technetium-99m-labeled anti-fibrin monoclonal antibody accumulation in an inflammatory focus. J Nucl Med. 1992;33:1181. [PubMed] [Google Scholar]
  • 13.Ishiwata I, Soma M, Ono I, Nakaguchi T, Ishiwata C, Nozawa S, Ishikawa H. Biological characteristics of adenocarcinoma cell line (HOUA-I) and B-lymphoblastoid cell line (HOUA-II) established from the same tissue of endometrial adenocarcinoma. Jikeikai Med J. 1989;36:303. [Google Scholar]
  • 14.Khazaeli MB, Saleh MN, Liu TP, Meredith RF, Wheeler RH, Baker TS, King D, Secher D, Allen L, Rogers K, Colcher D, Schlom J, Shochat D, LoBuglio AF. Pharmacokinetics and immune response of131I-chimeric mouse/human B72.3 (human γ4) monoclonal antibody in humans. Cancer Res. 1991;51:5461. [PubMed] [Google Scholar]
  • 15.Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA., Jr Determination of immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods. 1978;72:101. doi: 10.1016/0022-1759(84)90435-6. [DOI] [PubMed] [Google Scholar]
  • 16.Mather SJ, Ellison D. Reduction-mediated technetium-99m labeling of monoclonal antibodies. J Nucl Med. 1990;31:692. [PubMed] [Google Scholar]
  • 17.Meredith RF, LoBuglio AF, Plott WE, Orr RA, Brezovich IA, Russell CD, Harvey EB, Yester MV, Wagner AJ, Spencer SA, Wheeler RH, Saleh MN, Rogers KJ, Polansky A, Salter MM, Khazaeli MB. Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG, κ 17-1A monoclonal antibody. J Nucl Med. 1991;32:1162. [PubMed] [Google Scholar]
  • 18.Morrison SL, Johnson MJ, Herzenberg LA, Oi TV. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci USA. 1984;81:6851. doi: 10.1073/pnas.81.21.6851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Muto MG, Lepisto EM, Van den Abbeele AD, Knapp RC, Kassis AI. Influence of human antimurine antibody on CA 125 levels in patients with ovarian cancer undergoing radioimmunotherapy or immunoscintigraphy with murine monoclonal antibody OC125. Am J Obstet Gynecol. 1989;161:1206. doi: 10.1016/0002-9378(89)90667-4. [DOI] [PubMed] [Google Scholar]
  • 20.Nishimura Y, Yokoyama M, Araki K, Ueda R, Kudo A, Watanabe T. Recombinant human-mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen. Cancer Res. 1987;47:999. [PubMed] [Google Scholar]
  • 21.Phillips J, Sikora K, Watson JV. Localization of glioma by a human monoclonal antibody. Lancet. 1982;2:1214. doi: 10.1016/s0140-6736(82)91225-9. [DOI] [PubMed] [Google Scholar]
  • 22.Reuland P, Winker KH, Heuchert T, Ruck P, Mueller-Schauenburg W, Weller S, Feine U. Detection of infection in postoperative orthopedic patients with technetium-99m-labeled monoclonal antibodies against granulocytes. J Nucl Med. 1991;32:2209. [PubMed] [Google Scholar]
  • 23.Saga T, Endo K, Koizumi M, Kawamura Y, Watanabe Y, Konishi J, Ueda R, Nishimura Y, Yokoyama M, Watanabe T. In vitro and in vivo properties of human/mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen. J Nucl Med. 1990;31:1077. [PubMed] [Google Scholar]
  • 24.Saga T, Ishiwata I, Endo K, Sakahara H, Koizumi M, Watanabe Y, Nakai T, Hosono M, Ishikawa H, Sawada M, Konishi J. An antibody-tumor model for the targeting of CA 125-producing gynecologic malignancies. Jpn J Cancer Res. 1990;81:1141. doi: 10.1111/j.1349-7006.1990.tb02526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Sahagan BG, Dorai H, Saltzgaber-Mullaer J, Toneguzzo F, Guindon CA, Lilly SP, McDonald KW, Morrissey DV, Stone BA, Davis GL, McIntosh PK, Moore GP. A genetically engineered murinc/human chimeric antibody retains specificity for human tumor associated antigen. J Immunol. 1986;137:1066. [PubMed] [Google Scholar]
  • 26.Sakahara H, Endo K, Nakashima T, Koizumi M, Ohta H, Torizuka K, Furukawa T, Ohmomo Y, Yokoyama A, Okada K, Yoshida O, Nishi S. Effect of DTPA conjugation on the binding activity and biodistribution of monoclonal antibodies against alpha-fetoprotein. J Nucl Med. 1985;26:750. [PubMed] [Google Scholar]
  • 27.Sakahara H, Endo K, Nakashima T, Koizumi M, Kunimatsu M, Kawamura Y, Ohta H, Nakamura T, Tanaka H, Kotoura Y, Yamamuro T, Hosoi S, Toyama S, Torizuka K. Localization of human osteogenic sarcoma xenografts in nude mice by a monoclonal antibody labeled with radioiodine and indium-111. J Nucl Med. 1987;28:342. [PubMed] [Google Scholar]
  • 28.Sakahara H, Reynolds JA, Carrasquillo JA, Lor ME, Maloney PJ, Lotze MT, Larson SM, Neumann RD. In vitro complex formation and biodistribution of mouse antitumor monoclonal antibody in cancer patients. J Nucl Med. 1989;30:1311. [PubMed] [Google Scholar]
  • 29.Sakamoto M. Cyto-biological and immunological characterization of a newly established cell line (TMCC-1) derived from human uterine cervical adenocarcinoma. J Tokyo Med Coll. 1988;46:925. [Google Scholar]
  • 30.Scatchard G. The attraction of proteins for small molecules and ions. Ann NY Acad Sci. 1949;51:660. [Google Scholar]
  • 31.Schwarz A, Steinstrasser A. A novel approach to Tc-99m-labeled monoclonal antibodies (abstract) J Nucl Med. 1987;28:721. [Google Scholar]
  • 32.Sikora K. Human hybridomas. New York Basel: Dekker; 1987. Human monoclonal antibodies to cancer cells; p. 159. [Google Scholar]

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