Cancer Immunology, Immunotherapy

, Volume 34, Issue 1, pp 63–69 | Cite as

Growth inhibition of murine mammary carcinoma by monoclonal IgE antibodies specific for the mammary tumor virus

  • Eva Nagy
  • Istvan Berczi
  • Alec H. Sehon
Original articles


Two IgE-producing hybridomas were established from spleen cells of Balb/c mice, which had been immunized with mouse mammary tumor virus (MMTV). These IgE monoclonal antibodies (mAbs) reacted specifically with the major envelope glycoprotein (gp36) of MMTV, as established by the immunoblot assay and by passive cutaneous anaphylaxis. The effect of the IgE mAbs (produced by clone A8) on the growth of the MMTV-secreting mammary adenocarcinoma H2712 was investigated in syngeneic C3H/HeJ mice. The mice were inoculated s.c. with either 105 (≈100 × LD50) or 106 (≈1000 × LD50) tumor cells and received repeated i.p. injections of 25 µg anti-gp36 IgE mAbs at 4-day intervals for 8 weeks. This treatment prevented the development of subcutaneous tumors in 50% of the animals. Similar protection was observed when the tumor cells (105/animal) were injected i.p. 4 days prior to the beginning of the i.p. treatment consisting of injections of 25 µg mAbs at 4-day intervals for 6 weeks. However, these mAbs did not protect C3H/HeJ mice against the MMTV-negative MA16/c carcinoma cells. Hence, these results support the view that IgE-mediated cytotoxic mechanisms may play an immunologically specific antitumor surveillance role and that laboratory-induced antitumor IgE mAbs have the potential of specific therapeutic agents for in vivo destruction of tumor cells.

Key words

Murine mammary tumor virus IgE, Protective antibodies Tumor immunity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allegra J, Lipton A, Harvey H, Luderer J, Brenner D, Mortel R, Demers L, Gillin M, White D, Trautlein J (1976) Decreased prevalence of immediate hypersensitivity (atopy) in a cancer population. Cancer Res 36: 3225PubMedGoogle Scholar
  2. 2.
    Arbesman CE, Wypych JI, Reisman RE (1973) Serum IgE in human diseases. In: Mechanisms in allergy, reagin-mediated hypersensitivity. Dekker, New York, p 163Google Scholar
  3. 3.
    Augustin R, Chandradasa KD (1971) IgE levels and allergic skin reactions in cancer and non-cancer patients. Int Arch Allergy Appl Immunol 41: 141PubMedGoogle Scholar
  4. 4.
    Bartholomaeus WM, Keast D (1972) Reaginic antibody to tumor and alloantigens in mice. Nature 239: 206Google Scholar
  5. 5.
    Berczi I, Holford-Strevens V, Warsi ZH, McMorris LS, Thorlakson RH, Thorlakson TH, Sehon AH (1983) Tumor-reactive IgE antibodies in plasma of patients with gastrointestinal carcinomas. Cancer Immunol Immunother 14: 180PubMedGoogle Scholar
  6. 6.
    Black MM, Leis HP (1971) Cellular responses to autologous breast cancer tissue. Correlation with stage and lymphoreticuloendothelial reactive. Cancer 28: 263PubMedGoogle Scholar
  7. 7.
    Black MM, Leis HP Jr (1973) Cellular responses to autologous breast cancer tissue. Sequential observations. Cancer 32: 384PubMedGoogle Scholar
  8. 8.
    Broom BC, Alexander P (1975) Rat tumor allografts evoke anaphylactic antibody responses. Immunology 28: 1033PubMedGoogle Scholar
  9. 9.
    Bross IDJ, Natarajan N (1972) Leukemia from low-level radiation. Identification of susceptible children. N Engl J Med 287: 107PubMedGoogle Scholar
  10. 10.
    Burtin C, Scheinmann P, Salomon JC, Lespinats G, Frayssinet C, Lebel B, Canu P (1981) Increased tissue histamine in tumour-bearing mice and rats. Br J Cancer 43: 684PubMedGoogle Scholar
  11. 11.
    Burtin C, Scheinmann P, Salomon JC, Lespinats G, Loisillier F, Canu P (1981) The influence of intraperitoneal injections of histmaines on tumor growth in fibrosarcoma-bearing mice. Cancer Lett 12: 195PubMedGoogle Scholar
  12. 12.
    Burtin C, Scheinmann P, Salomon JC, Lespinats G, Canu P (1982) Decrease in tumour growth by injections of histamine or serotonin in fibrosarcoma bearing mice: influence of H1 and H2 histamine receptors. Br J Cancer 45: 54PubMedGoogle Scholar
  13. 13.
    Burtin C, Noirot C, Paupe J, Scheinmann P (1983) Decreased blood histamine levels in patients with solid malignant tumours. Br J Cancer 47: 367PubMedGoogle Scholar
  14. 14.
    Burtin C, Ponvert C, Fray A, Scheinmann P, Lespinats G, Loridon B, Canu P, Paupe J (1985) Inverse correlation between tumor incidence and tissue histamine levels in W/W/, W/+ and +/+ mice. JNCI 74: 671PubMedGoogle Scholar
  15. 15.
    Capron M (1988) Eosinophils in diseases: receptors and mediators: In: Progress in allergy and clinical immunology (Proc. 13th Int Cong Allergy Clin Immunol). Hogrefe & Huber, Toronto, p 6Google Scholar
  16. 16.
    Chaudhary VK (1990) A rapid method of cloning functional variable-region antibody genes inE. coli as single chain immunotoxins. Second Int Symp Immunotoxins, Lake Buena Vista, Fla.Google Scholar
  17. 17.
    Conrad DH (1989) Low affinity IgE (FcE R II) receptors. Clin Rev Allergy 7: 165PubMedGoogle Scholar
  18. 18.
    Daams JH, Hageman P, Calafat J, Bentvelzen P (1973) Antigenic structure of murine mammary tumour viruses. Eur J Cancer 9: 567PubMedGoogle Scholar
  19. 19.
    Fisherman EW (1960) Does the allergic diathesis influence malignancy? J Allergy 31: 74PubMedGoogle Scholar
  20. 20.
    Galfre G, Milstein C (1981) Preparation of monoclonal antibodies: strategies and procedures. Methods Enzymol 73: 1PubMedGoogle Scholar
  21. 21.
    Gershoni JM (1987) Protein blotting: a manual. Methods Biochem Anal 33: 1Google Scholar
  22. 22.
    Grace JT, Kondo T (1958) Investigations of host resistance in cancer patients. Ann Surg 148: 633PubMedGoogle Scholar
  23. 23.
    Haba S, Ovary Z, Nisonoff A (1985) Clearance of IgE from serum of normal and hybridoma-bearing mice. J Immunol 134: 3291PubMedGoogle Scholar
  24. 24.
    Hirano T, Hom C, Ovary Z (1983) Half life of murine IgE antibodies in the mouse. Int Arch Allergy Appl Immunol 71: 182PubMedGoogle Scholar
  25. 25.
    Hoogenraad N, Helman T, Hoogenraad J (1983) The effect of preinjection of mice with pristane on ascites tumour formation and monoclonal antibody production. J Immunol Methods 61: 317PubMedGoogle Scholar
  26. 26.
    Jacobs D, Landon J, Houri M, Merrett TG (1972) Circulating levels of immunoglobulin E in patients with cancer. Lancet II: 1059Google Scholar
  27. 27.
    Keller R, Ogilvie BM, Simpson E (1971) Tumour growth in nemotode-infected animals. Lancet I: 678Google Scholar
  28. 28.
    Kelly KA, Lang GM, Bundesen PG, Holford-Strevens V, Bottcher I, Sehon AH (1980) The development of a radioallergosorbent test (RAST) for murine IgE antibodies. J Immunol Methods 39: 317PubMedGoogle Scholar
  29. 29.
    Kenten JH, Molgaard HV, Houghton M, Derbyshire, RB, Viney J, Bell LO, Gould H (1982) Cloning and sequence determination of the gene for the human immunoglobulin ε chain expressed in a myeloma cell line. Proc Natl Acad Sci USA 79: 6661PubMedGoogle Scholar
  30. 30.
    Kenten J, Helm B, Ishizaka T, Cattini P, Gould H (1984) Properties of a human immunoglobulin ε-chain fragment synthesized inEscherichia coli. Proc Natl Acad Sci USA 81: 2955PubMedGoogle Scholar
  31. 31.
    Kernan NA, Byers V, Scannon PJ, Mischak RP, Brochstein MD, Flomenberg N, Dupont B, O'Reilly RJ (1988) Treatment of steroidresistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin. J Am Med Assoc 259: 3154Google Scholar
  32. 32.
    Lee N, Zhang SQ, Testa D (1988) A rapid multicolor Western blot. J Immunol Methods 106: 27PubMedGoogle Scholar
  33. 33.
    Likhite VV (1974) The delayed and lasting rejection of mammary adenocarcinoma cell tumors in DBA/2 mice with use of killedBordetella pertussis. Cancer Res 34: 1027PubMedGoogle Scholar
  34. 34.
    Liu F-T, Bohn JW, Ferry EL, Yamamoto H, Molinardo CA, Sherman LA, Klinman NR, Katz DH (1980) Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol 124: 2728PubMedGoogle Scholar
  35. 35.
    Logan J, Saker DN (1953) The incidence of allergic disorders in cancer. NZ Med J 52: 210Google Scholar
  36. 36.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265PubMedGoogle Scholar
  37. 37.
    Lynch NR, Salomon JC (1977) Passive local anaphylaxis: demonstration of antitumor activity and complementation of intratumor BCG. JNCI 58: 1093PubMedGoogle Scholar
  38. 38.
    Maiti PK, Lang GM, Sehon AH (1988) Tolerogenic conjugates of xenogeneic monoclonal antibodies with monomethoxypolyethylene glycol: I. Induction of long-lasting tolerance to xenogeneic monoclonal antibodies. Int J Cancer [Suppl] 3: 17Google Scholar
  39. 39.
    McKay WD (1966) The incidence of allergic disorders and cancer. Br J Cancer 20: 434PubMedGoogle Scholar
  40. 40.
    Meers PD (1973) Allergy and cancer. Lancet I: 884Google Scholar
  41. 41.
    Metzger H (1988) Molecular aspects of receptors and binding factors for IgE. Adv Immunol 43: 277PubMedGoogle Scholar
  42. 42.
    Reichmann L, Clark M, Waldmann H, Winter G (1988) Reshaping human antibodies for therapy. Nature 332: 323PubMedGoogle Scholar
  43. 43.
    Scheinmann P, Lebel B, Lynch NR, Salomon JC, Paupe JR, Burtin C (1979) Histamine levels in blood and other tissues of male and female C3H mice: II. Mice carrying a 3-methyl-cholanthrene-induced tumor. Agents Action 9: 95Google Scholar
  44. 44.
    Sehon AH (1982) Suppression of IgE antibody responses with tolerogenic conjugates of allergens and haptens. Prog Allergy 32: 161PubMedGoogle Scholar
  45. 45.
    Shoenfeld Y, Amnon H, Tal R, Smorodinsky NI, Lavie G, Mor C, Schteren S, Mammon Z, Pinkhas J, Keydar T (1987) Human monoclonal antibodies derived from lymph nodes of a patient with breast carcinoma react with MuMTV polypeptides. Cancer 59: 43PubMedGoogle Scholar
  46. 46.
    Stage DE, Mannik M (1974) Covalent binding of molecules to CNBr-activated agarose: parameters relevant to the activation and coupling reactons. Biochem Biophys Res Commun 343: 382Google Scholar
  47. 47.
    Sweeney WT, Seibel HR (1973) Histamine release from peritoneal mast cells of tumor susceptible rats following periods of tumor growth and sensitization with tumor antigen andB. pertussis. Int Arch Allergy 45: 789PubMedGoogle Scholar
  48. 48.
    Tsang VCW, Peralta JM, Simons AR (1983) Enzyme-linked immunoelectro-transfer blot techniques (EITB) for studying the specificities of antigens and antibodies separated by gel electrophoresis. Methods Enzymol 92: 377PubMedGoogle Scholar
  49. 49.
    Waldmann TA, Bull JM, Bruce RM, Broder S, Jost MC, Balestra ST, Suer ME (1974) Serum immunoglobulin E levels in patients with neoplastic disease. J Immunol 113: 379PubMedGoogle Scholar
  50. 50.
    Weatherly NF (1970) Increased survival of Swiss mice given sublethal injections ofTrichinella spiralis. J Parasitol 56: 748PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Eva Nagy
    • 1
  • Istvan Berczi
    • 1
  • Alec H. Sehon
    • 1
  1. 1.MRC Group for Allergy Research, Department of Immunology, Faculty of MedicineThe University of Manitoba WinnipegWinnipegCanada

Personalised recommendations