Skip to main content
NCBI home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1991 Jan;34(1):63–69. doi: 10.1007/BF01741326

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

Eva Nagy 1, Istvan Berczi 1, Alec H Sehon 1,✉
PMCID: PMC11038961  PMID: 1662114

Abstract

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

References

  • 1.Allegra J, Lipton A, Harvey H, Luderer J, Brenner D, Mortel R, Demers L, Gillin M, White D, Trautlein J. Decreased prevalence of immediate hypersensitivity (atopy) in a cancer population. Cancer Res. 1976;36:3225. [PubMed] [Google Scholar]
  • 2.Arbesman CE, Wypych JI, Reisman RE. Mechanisms in allergy, reagin-mediated hypersensitivity. New York: Dekker; 1973. Serum IgE in human diseases; p. 163. [Google Scholar]
  • 3.Augustin R, Chandradasa KD. IgE levels and allergic skin reactions in cancer and non-cancer patients. Int Arch Allergy Appl Immunol. 1971;41:141. doi: 10.1159/000230505. [DOI] [PubMed] [Google Scholar]
  • 4.Bartholomaeus WM, Keast D. Reaginic antibody to tumor and alloantigens in mice. Nature. 1972;239:206. doi: 10.1038/newbio239206a0. [DOI] [PubMed] [Google Scholar]
  • 5.Berczi I, Holford-Strevens V, Warsi ZH, McMorris LS, Thorlakson RH, Thorlakson TH, Sehon AH. Tumor-reactive IgE antibodies in plasma of patients with gastrointestinal carcinomas. Cancer Immunol Immunother. 1983;14:180. doi: 10.1007/BF00205357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Black MM, Leis HP. Cellular responses to autologous breast cancer tissue. Correlation with stage and lymphoreticuloendothelial reactive. Cancer. 1971;28:263. doi: 10.1002/1097-0142(197108)28:2<263::aid-cncr2820280202>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  • 7.Black MM, Leis HP., Jr Cellular responses to autologous breast cancer tissue. Sequential observations. Cancer. 1973;32:384. doi: 10.1002/1097-0142(197308)32:2<384::aid-cncr2820320215>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  • 8.Broom BC, Alexander P. Rat tumor allografts evoke anaphylactic antibody responses. Immunology. 1975;28:1033. [PMC free article] [PubMed] [Google Scholar]
  • 9.Bross IDJ, Natarajan N. Leukemia from low-level radiation. Identification of susceptible children. N Engl J Med. 1972;287:107. doi: 10.1056/NEJM197207202870301. [DOI] [PubMed] [Google Scholar]
  • 10.Burtin C, Scheinmann P, Salomon JC, Lespinats G, Frayssinet C, Lebel B, Canu P. Increased tissue histamine in tumour-bearing mice and rats. Br J Cancer. 1981;43:684. doi: 10.1038/bjc.1981.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Burtin C, Scheinmann P, Salomon JC, Lespinats G, Loisillier F, Canu P. The influence of intraperitoneal injections of histmaines on tumor growth in fibrosarcoma-bearing mice. Cancer Lett. 1981;12:195. doi: 10.1016/0304-3835(81)90068-9. [DOI] [PubMed] [Google Scholar]
  • 12.Burtin C, Scheinmann P, Salomon JC, Lespinats G, Canu P. Decrease in tumour growth by injections of histamine or serotonin in fibrosarcoma bearing mice: influence of H1 and H2 histamine receptors. Br J Cancer. 1982;45:54. doi: 10.1038/bjc.1982.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Burtin C, Noirot C, Paupe J, Scheinmann P. Decreased blood histamine levels in patients with solid malignant tumours. Br J Cancer. 1983;47:367. doi: 10.1038/bjc.1983.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Burtin C, Ponvert C, Fray A, Scheinmann P, Lespinats G, Loridon B, Canu P, Paupe J. Inverse correlation between tumor incidence and tissue histamine levels in W/W/, W/+ and +/+ mice. JNCI. 1985;74:671. [PubMed] [Google Scholar]
  • 15.Capron M. Progress in allergy and clinical immunology (Proc. 13th Int Cong Allergy Clin Immunol) Toronto: Hogrefe & Huber; 1988. Eosinophils in diseases: receptors and mediators; p. 6. [Google Scholar]
  • 16.Chaudhary VK. A rapid method of cloning functional variable-region antibody genes inE. coli as single chain immunotoxins. Lake Buena Vista, Fla.: Second Int Symp Immunotoxins; 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Conrad DH. Low affinity IgE (FcE R II) receptors. Clin Rev Allergy. 1989;7:165. doi: 10.1007/BF02914465. [DOI] [PubMed] [Google Scholar]
  • 18.Daams JH, Hageman P, Calafat J, Bentvelzen P. Antigenic structure of murine mammary tumour viruses. Eur J Cancer. 1973;9:567. doi: 10.1016/0014-2964(73)90146-1. [DOI] [PubMed] [Google Scholar]
  • 19.Fisherman EW. Does the allergic diathesis influence malignancy? J Allergy. 1960;31:74. doi: 10.1016/0021-8707(60)90026-5. [DOI] [PubMed] [Google Scholar]
  • 20.Galfre G, Milstein C. Preparation of monoclonal antibodies: strategies and procedures. Methods Enzymol. 1981;73:1. doi: 10.1016/0076-6879(81)73054-4. [DOI] [PubMed] [Google Scholar]
  • 21.Gershoni JM. Protein blotting: a manual. Methods Biochem Anal. 1987;33:1. doi: 10.1002/9780470110546.ch1. [DOI] [PubMed] [Google Scholar]
  • 22.Grace JT, Kondo T. Investigations of host resistance in cancer patients. Ann Surg. 1958;148:633. doi: 10.1097/00000658-195810000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Haba S, Ovary Z, Nisonoff A. Clearance of IgE from serum of normal and hybridoma-bearing mice. J Immunol. 1985;134:3291. [PubMed] [Google Scholar]
  • 24.Hirano T, Hom C, Ovary Z. Half life of murine IgE antibodies in the mouse. Int Arch Allergy Appl Immunol. 1983;71:182. doi: 10.1159/000233385. [DOI] [PubMed] [Google Scholar]
  • 25.Hoogenraad N, Helman T, Hoogenraad J. The effect of preinjection of mice with pristane on ascites tumour formation and monoclonal antibody production. J Immunol Methods. 1983;61:317. doi: 10.1016/0022-1759(83)90225-9. [DOI] [PubMed] [Google Scholar]
  • 26.Jacobs D, Landon J, Houri M, Merrett TG. Circulating levels of immunoglobulin E in patients with cancer. Lancet. 1972;II:1059. doi: 10.1016/s0140-6736(72)92341-0. [DOI] [PubMed] [Google Scholar]
  • 27.Keller R, Ogilvie BM, Simpson E. Tumour growth in nemotode-infected animals. Lancet. 1971;I:678. doi: 10.1016/s0140-6736(71)92683-3. [DOI] [PubMed] [Google Scholar]
  • 28.Kelly KA, Lang GM, Bundesen PG, Holford-Strevens V, Bottcher I, Sehon AH. The development of a radioallergosorbent test (RAST) for murine IgE antibodies. J Immunol Methods. 1980;39:317. doi: 10.1016/0022-1759(80)90232-x. [DOI] [PubMed] [Google Scholar]
  • 29.Kenten JH, Molgaard HV, Houghton M, Derbyshire RB, Viney J, Bell LO, Gould H. Cloning and sequence determination of the gene for the human immunoglobulin ε chain expressed in a myeloma cell line. Proc Natl Acad Sci USA. 1982;79:6661. doi: 10.1073/pnas.79.21.6661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Kenten J, Helm B, Ishizaka T, Cattini P, Gould H. Properties of a human immunoglobulin ε-chain fragment synthesized inEscherichia coli . Proc Natl Acad Sci USA. 1984;81:2955. doi: 10.1073/pnas.81.10.2955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Kernan NA, Byers V, Scannon PJ, Mischak RP, Brochstein MD, Flomenberg N, Dupont B, O'Reilly RJ. 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. 1988;259:3154. [PubMed] [Google Scholar]
  • 32.Lee N, Zhang SQ, Testa D. A rapid multicolor Western blot. J Immunol Methods. 1988;106:27. doi: 10.1016/0022-1759(88)90267-0. [DOI] [PubMed] [Google Scholar]
  • 33.Likhite VV. The delayed and lasting rejection of mammary adenocarcinoma cell tumors in DBA/2 mice with use of killedBordetella pertussis . Cancer Res. 1974;34:1027. [PubMed] [Google Scholar]
  • 34.Liu F-T, Bohn JW, Ferry EL, Yamamoto H, Molinardo CA, Sherman LA, Klinman NR, Katz DH. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980;124:2728. [PubMed] [Google Scholar]
  • 35.Logan J, Saker DN. The incidence of allergic disorders in cancer. NZ Med J. 1953;52:210. [PubMed] [Google Scholar]
  • 36.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265. [PubMed] [Google Scholar]
  • 37.Lynch NR, Salomon JC. Passive local anaphylaxis: demonstration of antitumor activity and complementation of intratumor BCG. JNCI. 1977;58:1093. doi: 10.1093/jnci/58.4.1093. [DOI] [PubMed] [Google Scholar]
  • 38.Maiti PK, Lang GM, Sehon AH. Tolerogenic conjugates of xenogeneic monoclonal antibodies with monomethoxypolyethylene glycol: I. Induction of long-lasting tolerance to xenogeneic monoclonal antibodies. Int J Cancer [Suppl] 1988;3:17. doi: 10.1002/ijc.2910410805. [DOI] [PubMed] [Google Scholar]
  • 39.McKay WD. The incidence of allergic disorders and cancer. Br J Cancer. 1966;20:434. doi: 10.1038/bjc.1966.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Meers PD. Allergy and cancer. Lancet. 1973;I:884. doi: 10.1016/s0140-6736(73)91452-9. [DOI] [PubMed] [Google Scholar]
  • 41.Metzger H. Molecular aspects of receptors and binding factors for IgE. Adv Immunol. 1988;43:277. doi: 10.1016/s0065-2776(08)60368-5. [DOI] [PubMed] [Google Scholar]
  • 42.Reichmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature. 1988;332:323. doi: 10.1038/332323a0. [DOI] [PubMed] [Google Scholar]
  • 43.Scheinmann P, Lebel B, Lynch NR, Salomon JC, Paupe JR, Burtin C. Histamine levels in blood and other tissues of male and female C3H mice: II. Mice carrying a 3-methyl-cholanthrene-induced tumor. Agents Action. 1979;9:95. doi: 10.1007/BF02024138. [DOI] [PubMed] [Google Scholar]
  • 44.Sehon AH. Suppression of IgE antibody responses with tolerogenic conjugates of allergens and haptens. Prog Allergy. 1982;32:161. [PubMed] [Google Scholar]
  • 45.Shoenfeld Y, Amnon H, Tal R, Smorodinsky NI, Lavie G, Mor C, Schteren S, Mammon Z, Pinkhas J, Keydar T. Human monoclonal antibodies derived from lymph nodes of a patient with breast carcinoma react with MuMTV polypeptides. Cancer. 1987;59:43. doi: 10.1002/1097-0142(19870101)59:1<43::aid-cncr2820590113>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  • 46.Stage DE, Mannik M. Covalent binding of molecules to CNBr-activated agarose: parameters relevant to the activation and coupling reactons. Biochem Biophys Res Commun. 1974;343:382. doi: 10.1016/0304-4165(74)90102-0. [DOI] [PubMed] [Google Scholar]
  • 47.Sweeney WT, Seibel HR. 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. 1973;45:789. doi: 10.1159/000231078. [DOI] [PubMed] [Google Scholar]
  • 48.Tsang VCW, Peralta JM, Simons AR. Enzyme-linked immunoelectro-transfer blot techniques (EITB) for studying the specificities of antigens and antibodies separated by gel electrophoresis. Methods Enzymol. 1983;92:377. doi: 10.1016/0076-6879(83)92032-3. [DOI] [PubMed] [Google Scholar]
  • 49.Waldmann TA, Bull JM, Bruce RM, Broder S, Jost MC, Balestra ST, Suer ME. Serum immunoglobulin E levels in patients with neoplastic disease. J Immunol. 1974;113:379. [PubMed] [Google Scholar]
  • 50.Weatherly NF. Increased survival of Swiss mice given sublethal injections ofTrichinella spiralis . J Parasitol. 1970;56:748. [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES