Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1985 Jun 1;161(6):1432–1449. doi: 10.1084/jem.161.6.1432

Suppression of in vivo tumor formation induced by simian virus 40- transformed cells in mice receiving antiidiotypic antibodies

PMCID: PMC2187644  PMID: 2409201

Abstract

This study characterizes four private idiotypes (Id) associated with monoclonal antibodies (mAb) to simian virus 40 (SV40) tumor antigen (T- Ag), and to a cellular protein, p53. Anti-Id recognized Id determinants associated with the antibody-combining site. BALB/c mice receiving a pool of anti-Id directed against mAb recognizing distinct amino and carboxyl terminal epitopes of T-Ag before receiving a tumorigenic dose of SV40-transformed cells showed suppression of tumor formation. Serum obtained from these mice before tumor challenge contained anti-anti-Id that failed to bind T-Ag. These data support the potential role of regulatory idiotopes in tumor immunity.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbas A. K., Perry L. L., Bach B. A., Greene M. I. Idiotype-specific T cell immunity. I. Generation of effector and suppressor T lymphocytes reactive with myeloma idiotypic determinants. J Immunol. 1980 Mar;124(3):1160–1166. [PubMed] [Google Scholar]
  2. Anderson J. L., Martin R. G., Chang C., Mora P. T., Livingston D. M. Nuclear preparations of SV40-transformed cells contain tumor-specific transplantation antigen activity. Virology. 1977 Jan;76(1):420–425. doi: 10.1016/0042-6822(77)90314-2. [DOI] [PubMed] [Google Scholar]
  3. Ball R. K., Siegl B., Quellhorst S., Brandner G., Braun D. G. Monoclonal antibodies against simian virus 40 nuclear large T tumour antigen: epitope mapping, papova virus cross-reaction and cell surface staining. EMBO J. 1984 Jul;3(7):1485–1491. doi: 10.1002/j.1460-2075.1984.tb02000.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bona C. A., Heber-Katz E., Paul W. E. Idiotype-anti-idiotype regulation. I. Immunization with a levan-binding myeloma protein leads to the appearance of auto-anti-(anti-idiotype) antibodies and to the activation of silent clones. J Exp Med. 1981 Apr 1;153(4):951–967. doi: 10.1084/jem.153.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang C., Martin R. G., Livingston D. M., Luborsky S. W., Hu C. P., Mora P. T. Relationship between T-antigen and tumor-specific transplantation antigen in simian virus 40-transformed cells. J Virol. 1979 Jan;29(1):69–75. doi: 10.1128/jvi.29.1.69-75.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daley M. J., Gebel H. M., Lynch R. G. Idiotype-specific transplantation resistance to MOPC-315: abrogation by post-immunization thymectomy. J Immunol. 1978 May;120(5):1620–1624. [PubMed] [Google Scholar]
  7. Deppert W., Hanke K., Henning R. Simian virus 40 T-antigen-related cell surface antigen: serological demonstration on simian virus 40-transformed monolayer cells in situ. J Virol. 1980 Aug;35(2):505–518. doi: 10.1128/jvi.35.2.505-518.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deppert W., Walter G. Domains of simian virus 40 large T-antigen exposed on the cell surface. Virology. 1982 Oct 15;122(1):56–70. doi: 10.1016/0042-6822(82)90377-4. [DOI] [PubMed] [Google Scholar]
  9. Dippold W. G., Jay G., DeLeo A. B., Khoury G., Old L. J. p53 transformation-related protein: detection by monoclonal antibody in mouse and human cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1695–1699. doi: 10.1073/pnas.78.3.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ertl H. C., Finberg R. W. Sendai virus-specific T-cell clones: induction of cytolytic T cells by an anti-idiotypic antibody directed against a helper T-cell clone. Proc Natl Acad Sci U S A. 1984 May;81(9):2850–2854. doi: 10.1073/pnas.81.9.2850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Flood P. M., Kripke M. L., Rowley D. A., Schreiber H. Suppression of tumor rejection by autologous anti-idiotypic immunity. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2209–2213. doi: 10.1073/pnas.77.4.2209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Flyer D. C., Tevethia S. S. Biology of simian virus 40 (SV40) transplantation antigen (TrAg). VIII. Retention of SV40 TrAg sites on purified SV40 large T antigen following denaturation with sodium dodecyl sulfate. Virology. 1982 Feb;117(1):267–270. doi: 10.1016/0042-6822(82)90527-x. [DOI] [PubMed] [Google Scholar]
  13. Francotte M., Urbain J. Induction of anti-tobacco mosaic virus antibodies in mice by rabbit antiidiotypic antibodies. J Exp Med. 1984 Nov 1;160(5):1485–1494. doi: 10.1084/jem.160.5.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fujimoto S., Greene M. I., Sehon A. H. Regulation of the immune response to tumor antigens. II. The nature of immunosuppressor cells in tumor-bearing hosts. J Immunol. 1976 Mar;116(3):800–806. [PubMed] [Google Scholar]
  15. Gershon R. K., Mokyr M. B., Mitchell M. S. Activation of suppressor T cells by tumour cells and specific antibody. Nature. 1974 Aug 16;250(467):594–596. doi: 10.1038/250594a0. [DOI] [PubMed] [Google Scholar]
  16. Glaser M. Regulation of specific cell-mediated cytotoxic response against SV40-induced tumor associated antigens by depletion of suppressor T cells with cyclophosphamide in mice. J Exp Med. 1979 Mar 1;149(3):774–779. doi: 10.1084/jem.149.3.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gorczynski R. M., Kennedy M., Polidoulis I., Price G. B. Altered tumor growth in vivo after immunization of mice with antitumor antibodies. Cancer Res. 1984 Aug;44(8):3291–3298. [PubMed] [Google Scholar]
  18. Harlow E., Crawford L. V., Pim D. C., Williamson N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol. 1981 Sep;39(3):861–869. doi: 10.1128/jvi.39.3.861-869.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  20. Kennedy R. C., Adler-Storthz K., Burns J. W., Sr, Henkel R. D., Dreesman G. R. Antiidiotype modulation of herpes simplex virus infection leading to increased pathogenicity. J Virol. 1984 Jun;50(3):951–953. doi: 10.1128/jvi.50.3.951-953.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kennedy R. C., Adler-Storthz K., Henkel R. D., Dreesman G. R. Characteristics of a shared idiotype by two IgM anti-herpes simplex virus monoclonal antibodies that recognize different determinants. J Immunol. 1983 Apr;130(4):1943–1946. [PubMed] [Google Scholar]
  22. Kennedy R. C., Adler-Storthz K., Henkel R. D., Sanchez Y., Melnick J. L., Dreesman G. R. Immune response to hepatitis B surface antigen: enhancement by prior injection of antibodies to the idiotype. Science. 1983 Aug 26;221(4613):853–855. doi: 10.1126/science.6603657. [DOI] [PubMed] [Google Scholar]
  23. Kennedy R. C., Dreesman G. R. Common idiotypic determinant associated with human antibodies to hepatitis B surface antigen. J Immunol. 1983 Jan;130(1):385–389. [PubMed] [Google Scholar]
  24. Kennedy R. C., Dreesman G. R. Enhancement of the immune response to hepatitis B surface antigen. In vivo administration of antiidiotype induces anti-HBs that expresses a similar idiotype. J Exp Med. 1984 Mar 1;159(3):655–665. doi: 10.1084/jem.159.3.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kennedy R. C., Dreesman G. R. Production and characterization of anti-idiotype reagents for the analysis of viral antigen systems. J Virol Methods. 1983 Aug;7(2):103–115. doi: 10.1016/0166-0934(83)90096-4. [DOI] [PubMed] [Google Scholar]
  26. Kennedy R. C., Ionescu-Matiu I., Adler-Storthz K., Henkel R. D., Sanchez Y., Dreesman G. R. Characterization of anti-hepatitis B surface antigen monoclonal antibodies. Intervirology. 1983;19(3):176–180. doi: 10.1159/000149354. [DOI] [PubMed] [Google Scholar]
  27. Kit S., Kurimura T., Dubbs D. R. Transplantable mouse tumor line induced by injection of SV40-transformed mouse kidney cells. Int J Cancer. 1969 Jul 15;4(4):384–392. doi: 10.1002/ijc.2910040403. [DOI] [PubMed] [Google Scholar]
  28. Koprowski H., Herlyn D., Lubeck M., DeFreitas E., Sears H. F. Human anti-idiotype antibodies in cancer patients: Is the modulation of the immune response beneficial for the patient? Proc Natl Acad Sci U S A. 1984 Jan;81(1):216–219. doi: 10.1073/pnas.81.1.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kresina T. F., Baine Y., Nisonoff A. Adoptive transfer of resistance to growth of an idiotype-secreting hybridoma by T cells from idiotypically suppressed mice. J Immunol. 1983 Mar;130(3):1478–1482. [PubMed] [Google Scholar]
  30. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  31. Lanford R. E., Butel J. S. Antigenic relationship of SV40 early proteins to purified large T polypeptide. Virology. 1979 Sep;97(2):295–306. doi: 10.1016/0042-6822(79)90341-6. [DOI] [PubMed] [Google Scholar]
  32. Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
  33. Luborsky S. W., Chang C., Pancake S. J., Mora P. T. Comparative behavior of simian virus 40 T-antigen and of tumor-specific surface and transplantation antigens during partial purification. Cancer Res. 1978 Aug;38(8):2367–2371. [PubMed] [Google Scholar]
  34. Lynch R. G., Graff R. J., Sirisinha S., Simms E. S., Eisen H. N. Myeloma proteins as tumor-specific transplantation antigens. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1540–1544. doi: 10.1073/pnas.69.6.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. McCormick F., Harlow E. Association of a murine 53,000-dalton phosphoprotein with simian virus 40 large-T antigen in transformed cells. J Virol. 1980 Apr;34(1):213–224. doi: 10.1128/jvi.34.1.213-224.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McNamara M. K., Ward R. E., Kohler H. Monoclonal idiotope vaccine against Streptococcus pneumoniae infection. Science. 1984 Dec 14;226(4680):1325–1326. doi: 10.1126/science.6505692. [DOI] [PubMed] [Google Scholar]
  37. Nepom G. T., Nelson K. A., Holbeck S. L., Hellström I., Hellström K. E. Induction of immunity to a human tumor marker by in vivo administration of anti-idiotypic antibodies in mice. Proc Natl Acad Sci U S A. 1984 May;81(9):2864–2867. doi: 10.1073/pnas.81.9.2864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nisonoff A., Lamoyi E. Implications of the presence of an internal image of the antigen in anti-idiotypic antibodies: possible application to vaccine production. Clin Immunol Immunopathol. 1981 Dec;21(3):397–406. doi: 10.1016/0090-1229(81)90228-2. [DOI] [PubMed] [Google Scholar]
  39. Noonan C. A., Butel J. S. Temperature-sensitive mutants of simian virus 40. I. Isolation aand preliminary characterization of B/C gene mutants. Intervirology. 1978;10(3):181–195. doi: 10.1159/000148982. [DOI] [PubMed] [Google Scholar]
  40. North R. J. Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med. 1982 Apr 1;155(4):1063–1074. doi: 10.1084/jem.155.4.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. O'Connell K. A., Gooding L. R. Cloned cytotoxic T lymphocytes recognize cells expressing discrete fragments of the SV40 tumor antigen. J Immunol. 1984 Feb;132(2):953–958. [PubMed] [Google Scholar]
  42. Perek Y., Hurwitz E., Burowski D., Haimovich J. Immunotherapy of a murine B cell tumor with antibodies and F(ab')2 fragments against idiotypic determinants of its cell surface IgM. J Immunol. 1983 Sep;131(3):1600–1603. [PubMed] [Google Scholar]
  43. Perry L. L., Greene M. I. T cell subset interactions in the regulation of syngeneic tumor immunity. Fed Proc. 1981 Jan;40(1):39–44. [PubMed] [Google Scholar]
  44. RAPP F., BUTEL J. S., MELNICK J. L. VIRUS-INDUCED INTRANUCLEAR ANTIGEN IN CELLS TRANSFORMED BY PAPOVAVIRUS SV40. Proc Soc Exp Biol Med. 1964 Aug-Sep;116:1131–1135. doi: 10.3181/00379727-116-29472. [DOI] [PubMed] [Google Scholar]
  45. Rapp F., Pauluzzi S., Butel J. S. Variation in properties of plaque progeny of PARA (defective simian papovavirus 40)-adenovirus 7. J Virol. 1969 Nov;4(5):626–631. doi: 10.1128/jvi.4.5.626-631.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Reagan K. J., Wunner W. H., Wiktor T. J., Koprowski H. Anti-idiotypic antibodies induce neutralizing antibodies to rabies virus glycoprotein. J Virol. 1983 Dec;48(3):660–666. doi: 10.1128/jvi.48.3.660-666.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Rodkey L. S. Autoregulation of immune responses via idiotype network interactions. Microbiol Rev. 1980 Dec;44(4):631–659. doi: 10.1128/mr.44.4.631-659.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sacks D. L., Esser K. M., Sher A. Immunization of mice against African trypanosomiasis using anti-idiotypic antibodies. J Exp Med. 1982 Apr 1;155(4):1108–1119. doi: 10.1084/jem.155.4.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sacks D. L., Kelsoe G. H., Sachs D. H. Induction of immune responses with anti-idiotypic antibodies: implications for the induction of protective immunity. Springer Semin Immunopathol. 1983;6(1):79–97. doi: 10.1007/BF01857368. [DOI] [PubMed] [Google Scholar]
  50. Santos M., Butel J. S. Antigenic structure of simian virus 40 large tumor antigen and association with cellular protein p53 on the surfaces of simian virus 40-infected and -transformed cells. J Virol. 1984 Aug;51(2):376–383. doi: 10.1128/jvi.51.2.376-383.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Santos M., Butel J. S. Association of SV40 large tumor antigen and cellular proteins on the surface of SV40-transformed mouse cells. Virology. 1982 Jul 15;120(1):1–17. doi: 10.1016/0042-6822(82)90002-2. [DOI] [PubMed] [Google Scholar]
  52. Schatten S., Drebin J. A., Perry L. L., Chung W., Greene M. I. Regulation of the immune response to tumor antigens. X. Activation of third-order suppressor T cells that abrogate anti-tumor immune responses. J Immunol. 1984 Aug;133(2):1064–1069. [PubMed] [Google Scholar]
  53. Schneider C., Newman R. A., Sutherland D. R., Asser U., Greaves M. F. A one-step purification of membrane proteins using a high efficiency immunomatrix. J Biol Chem. 1982 Sep 25;257(18):10766–10769. [PubMed] [Google Scholar]
  54. Sharpe A. H., Gaulton G. N., McDade K. K., Fields B. N., Greene M. I. Syngeneic monoclonal antiidiotype can induce cellular immunity to reovirus. J Exp Med. 1984 Oct 1;160(4):1195–1205. doi: 10.1084/jem.160.4.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Soule H. R., Butel J. S. Subcellular Localization of simian virus 40 large tumor antigen. J Virol. 1979 May;30(2):523–532. doi: 10.1128/jvi.30.2.523-532.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Soule H. R., Lanford R. E., Butel J. S. Antigenic and immunogenic characteristics of nuclear and membrane-associated simian virus 40 tumor antigen. J Virol. 1980 Feb;33(2):887–901. doi: 10.1128/jvi.33.2.887-901.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Stein K. E., Söderström T. Neonatal administration of idiotype or antiidiotype primes for protection against Escherichia coli K13 infection in mice. J Exp Med. 1984 Oct 1;160(4):1001–1011. doi: 10.1084/jem.160.4.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Stevenson F. K., Gordon J. Immunization with idiotypic immunoglobulin protects against development of B lymphocytic leukemia, but emerging tumor cells can evade antibody attack by modulation. J Immunol. 1983 Feb;130(2):970–973. [PubMed] [Google Scholar]
  59. Stevenson G. T., Stevenson F. K. Treatment of lymphoid tumors with anti-idiotype antibodies. Springer Semin Immunopathol. 1983;6(1):99–115. doi: 10.1007/BF01857369. [DOI] [PubMed] [Google Scholar]
  60. Sugai S., Palmer D. W., Talal N., Witz I. P. Protective and cellular immune responses to idiotypic determinants on cells from a spontaneous lymphoma of NZB-NZW F1 mice. J Exp Med. 1974 Dec 1;140(6):1547–1558. doi: 10.1084/jem.140.6.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sy M. S., Bach B. A., Dohi Y., Nisonoff A., Benacerraf B., Greene M. I. Antigen- and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies. J Exp Med. 1979 Nov 1;150(5):1216–1228. doi: 10.1084/jem.150.5.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tevethia S. S., Tevethia M. J., Lewis A. J., Reddy V. B., Weissman S. M. Biology of simian virus 40 (SV40) transplantation antigen (TrAg). IX. Analysis of TrAg in mouse cells synthesizing truncated SV40 large T antigen. Virology. 1983 Jul 30;128(2):319–330. doi: 10.1016/0042-6822(83)90259-3. [DOI] [PubMed] [Google Scholar]
  63. Tilkin A. F., Schaaf-Lafontaine N., Van Acker A., Boccadoro M., Urbain J. Reduced tumor growth after low-dose irradiation or immunization against blastic suppressor T cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1809–1812. doi: 10.1073/pnas.78.3.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Urbain J., Wuilmart C., Cazenave P. A. Idiotypic regulation in immune networks. Contemp Top Mol Immunol. 1981;8:113–148. doi: 10.1007/978-1-4684-3917-5_4. [DOI] [PubMed] [Google Scholar]
  65. Zarling J. M., Tevethia S. S. Transplantation immunity to simian virus 40-transformed cells in tumor-bearing mice. I. Development of cellular immunity to simian virus 40 tumor-specific transplantation antigens during tumorigenesis by transplanted cells. J Natl Cancer Inst. 1973 Jan;50(1):137–147. doi: 10.1093/jnci/50.1.137. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES