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. 1987 Apr;24(2):127–132. doi: 10.1007/BF00205589

Construction and characterisation of a hybrid-hybrid monoclonal antibody recognising both carcinoembryonic antigen (CEA) and vinca alkaloids

J R F Corvalan 1,✉, W Smith 1
PMCID: PMC11038046  PMID: 3829046

Abstract

Recent developments of hybridoma technology have allowed us to prepare a bispecific monoclonal antibody recognising both the tumour-associated antigen carcinoembryonic antigen (CEA) and the cytostatic vinca alkaloids. The yields of the hybrid-hybrid 28.19.8 monclonal after affinity chromatography purification are close to 50% of the total Ig produced.

The hybrid-hybrid has a molecular weight ca. 150000 daltons. The heavy chains of the hybrid-hybrid are a γ1 heavy chain from the parental anti-CEA monoclonal and a γ2a heavy chain from the anti-vinca alkaloid donor lymphocytes.

Keywords: Molecular Weight, Monoclonal Antibody, Cancer Research, Alkaloid, Heavy Chain

References

  • 1.Avrameas S. Coupling of enzymes to proteins with glutaraldehyde. Immunochemistry. 1969;6:43. doi: 10.1016/0019-2791(69)90177-3. [DOI] [PubMed] [Google Scholar]
  • 2.Baldwin RW, Byers VS (eds) (1985) In: Monoclonal antibodies for cancer detection and therapy. Academic Press
  • 3.Boulianne G, Hozumi N, Shulman MJ. Production of functional chimaeric mouse/human antibody. Nature. 1984;312:643. doi: 10.1038/312643a0. [DOI] [PubMed] [Google Scholar]
  • 4.Buchegger F, Haskel CM, Schreyer M, Scazziga BR, Randin S, Carrel S, Mach JP. Radiolabelled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice. J Exp Med. 1983;158:413. doi: 10.1084/jem.158.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Cobbold SP, Waldmann H. Therapeutic potential of monovalent monoclonal antibodies. Nature. 1984;308:460. doi: 10.1038/308460a0. [DOI] [PubMed] [Google Scholar]
  • 6.Corvalan JRF, Axton CA, Brandon DR, Smith W, Woodhouse CS. Classification of anti-CEA monoclonal antibodies. Protides of the Biol Fluids. 1984;31:921. [Google Scholar]
  • 7.Gatter KC, Abdulaziz Z, Beverley P, Corvalan JRF, Ford C, Lane EB, Mota M, Nash JRG, Pulford K, Stein H, Taylor-Papadimitriou J, Woodhouse C, Mason DY. Use of monoclonal antibodies for the histopathological diagnosis of human malignancy. J Clin Pathol. 1982;35:1253. doi: 10.1136/jcp.35.11.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Hellstrom I, Hellstrom KE, Yeh M. Lymphocyte-dependent antibodies to antigen 3.1, a cell-surface antigen expressed by a subgroup of human melanomas. Int J Cancer. 1981;27:281. doi: 10.1002/ijc.2910270305. [DOI] [PubMed] [Google Scholar]
  • 9.Herlyn D, Koprowski H. IgG2a monoclonal antibodies inhibit tumour growth through interaction with effector cells. Proc Natl Acad Sci USA. 1982;79:4761. doi: 10.1073/pnas.79.15.4761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Hockey M, Ford C, Newman C, Corvalan JRF, Rowland GF, Stokes H, Thompson H, Fielding JWL. The immunohistochemical localisation of carcinoembryonic antigen (CEA) with monoclonal antibody in gastric adenocarcinomas. Br J Surg. 1983;70:300. [Google Scholar]
  • 11.Horan Hand P, Nuti M, Colcher D, Schlom J. Antigenic heterogeneity of human mammary carcinoma cells defined by monoclonal antibodies. Protides of the Biol Fluids. 1984;31:809. [Google Scholar]
  • 12.Imai K, Pellegrino MA, Wilson BS, Ferrone S. Higher cytolytic efficiency of an IgG2a than of an IgG1 monoclonal antibody reacting with the same (or spatially close) determinant on a human high molecular weight melanoma-associated antigen. Cell Immunol. 1982;72:239. doi: 10.1016/0008-8749(82)90472-5. [DOI] [PubMed] [Google Scholar]
  • 13.Kipps TJ, Parham P, Punt J, Herzenberg LA. Importance of immunoglobulin isotype in human antibody-dependent, cell-mediated cytotoxicity directed by murine monoclonal antibodies. J Exp Med. 1985;161:1. doi: 10.1084/jem.161.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  • 15.Lewis JCM, Boxer GM, Searle F, Bagshawe KD. The comparative distribution of monoclonal antibodies to CEA in colorectal xenografts. Tumour Biol. 1984;5:255. [PubMed] [Google Scholar]
  • 16.Martinis J, Kull JF, Franz G, Bartholomew RM. Monoclonal antibodies with dual antigen specificity. Protides of the Biol Fluids. 1982;30:311. [Google Scholar]
  • 17.Milstein C, Cuello AC. Hybrid hybridomas and their use in immunohistochemistry. Nature. 1983;305:537. doi: 10.1038/305537a0. [DOI] [PubMed] [Google Scholar]
  • 18.Morrison SL, Johnson MJ, Herzenberg LA, Oi VT. 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.Neuberger MS, Williams GT, Fox RO. Recombinant antibodies possessing novel effector functions. Nature. 1984;312:604. doi: 10.1038/312604a0. [DOI] [PubMed] [Google Scholar]
  • 20.Pimm M, Armitage NC, Perkins AC, Smith W, Baldwin RW. Localisation of an anti-CEA monoclonal antibody in colorectal carcinoma. Cancer Immunol Immunother. 1985;19:8. doi: 10.1007/BF00199305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Rowland GF, Axton CA, Baldwin RW, Brown JR, Corvalan JRF, Embleton MJ, Gore VA, Hellstrom I, Hellstrom KE, Jacobs E, Marsden CH, Pimm MV, Simmonds RG, Smith W. Antitumour properties of vindesine-monoclonal antibody conjugates. Cancer Immunol Immunother. 1985;19:1. doi: 10.1007/BF00199304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Rowland GR, Simmonds RG, Gore VA, Marsden CH, Smith W. Drug localisation and growth inhibition studies of vindesine-monoclonal anti-CEA conjugates in a human tumour xenograft. Cancer Immunol Immunother. 1986;21:183. doi: 10.1007/BF00199359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Simonds RG, Smith W, Marsden CH. 3-Phenylaso-4-hydroxy-phenylisothiocyanates: reagents for efficient haptenation of immunoglobulin and other carrier molecules. J Immunol Methods. 1982;54:23. doi: 10.1016/0022-1759(82)90109-0. [DOI] [PubMed] [Google Scholar]
  • 24.Simmonds RG, Smith W, Corvalan JRF. Affinity purification of anti-CEA antibody. Protides of the Biol Fluids. 1984;31:917. [Google Scholar]
  • 25.Steplewski Z, Lubeck MD, Koprowski H. Human marcophages armed with murine immunoglobulin G2a antibodies to tumour destroy human cancer cells. Science. 1983;221:865. doi: 10.1126/science.6879183. [DOI] [PubMed] [Google Scholar]

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