Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Feb;91(2):266–271. doi: 10.1111/j.1365-2249.1993.tb05893.x

Immunization of mice with baculovirus-derived recombinant SV40 large tumour antigen induces protective tumour immunity to a lethal challenge with SV40-transformed cells.

M H Shearer 1, R K Bright 1, R E Lanford 1, R C Kennedy 1
PMCID: PMC1554672  PMID: 7679059

Abstract

In this study, we examined the humoral immune responses and in vivo tumour immunity induced by baculovirus recombinant simian virus 40 (SV40) large tumour antigen (rSV40 T-ag). BALB/c mice immunized with rSV40 T-ag produced antibody responses that recognized SV40 large tumour antigen (T-ag) by ELISA. Analysis of these anti-SV40 T-ag responses indicated that the antibodies recognized epitopes associated with both the carboxy and amino terminus of SV40 T-ag. This pattern of SV40 T-ag epitope recognition was similar to that observed in anti-SV40 T-ag responses induced by inoculation with irradiated SV40-transformed cells. Mice immunized with either rSV40 T-ag or with the inactivated transformed cells were protected from a subsequent in vivo lethal tumour challenge with live SV40-transformed cells. These studies suggest that humoral immune responses induced by rSV40 T-ag are similar in epitope specificity to that induced by inactivated SV40-transformed cells. In addition, recombinant tumour-specific antigens from papovaviruses, such as SV40, can be used to induce tumour immunity which protects from a subsequent lethal tumour challenge. This study may provide insight into the use of recombinant tumour antigens as putative tumour vaccines and in the development of active immunotherapeutic strategies for treating virus-induced cancers.

Full text

PDF
266

Selected References

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

  1. 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]
  2. Baker S. J., Fearon E. R., Nigro J. M., Hamilton S. R., Preisinger A. C., Jessup J. M., vanTuinen P., Ledbetter D. H., Barker D. F., Nakamura Y. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. doi: 10.1126/science.2649981. [DOI] [PubMed] [Google Scholar]
  3. Bolognesi D. P. HIV immunization. Fresh pathways to follow. Nature. 1990 Apr 26;344(6269):818–819. doi: 10.1038/344818a0. [DOI] [PubMed] [Google Scholar]
  4. Butel J. S., Jarvis D. L. The plasma-membrane-associated form of SV40 large tumor antigen: biochemical and biological properties. Biochim Biophys Acta. 1986 Oct 28;865(2):171–195. doi: 10.1016/0304-419x(86)90027-2. [DOI] [PubMed] [Google Scholar]
  5. Butel J. S., Tevethia S. S., Melnick J. L. Oncogenicity and cell transformation by papovavirus SV40: the role of the viral genome. Adv Cancer Res. 1972;15:1–55. doi: 10.1016/s0065-230x(08)60371-1. [DOI] [PubMed] [Google Scholar]
  6. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  7. DeCaprio J. A., Ludlow J. W., Figge J., Shew J. Y., Huang C. M., Lee W. H., Marsilio E., Paucha E., Livingston D. M. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988 Jul 15;54(2):275–283. doi: 10.1016/0092-8674(88)90559-4. [DOI] [PubMed] [Google Scholar]
  8. Dörries K., Loeber G., Meixensberger J. Association of polyomaviruses JC, SV40, and BK with human brain tumors. Virology. 1987 Sep;160(1):268–270. doi: 10.1016/0042-6822(87)90071-7. [DOI] [PubMed] [Google Scholar]
  9. Ey P. L., Prowse S. J., Jenkin C. R. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978 Jul;15(7):429–436. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
  10. Gooding L. R. Specificities of killing by T lymphocytes generated against syngeneic SV40 transformants: studies employing recombinants within the H-2 complex. J Immunol. 1979 Mar;122(3):1002–1008. [PubMed] [Google Scholar]
  11. Gooding L. R. Specificities of killing by cytotoxic lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells. J Immunol. 1977 Mar;118(3):920–927. [PubMed] [Google Scholar]
  12. Harbour J. W., Lai S. L., Whang-Peng J., Gazdar A. F., Minna J. D., Kaye F. J. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science. 1988 Jul 15;241(4863):353–357. doi: 10.1126/science.2838909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Knowles B. B., Koncar M., Pfizenmaier K., Solter D., Aden D. P., Trinchieri G. Genetic control of the cytotoxic T cell response to SV40 tumor-associated specific antigen. J Immunol. 1979 May;122(5):1798–1806. [PubMed] [Google Scholar]
  16. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Krieg P., Scherer G. Cloning of SV40 genomes from human brain tumors. Virology. 1984 Oct 30;138(2):336–340. doi: 10.1016/0042-6822(84)90357-x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Lanford R. E. Expression of simian virus 40 T antigen in insect cells using a baculovirus expression vector. Virology. 1988 Nov;167(1):72–81. doi: 10.1016/0042-6822(88)90055-4. [DOI] [PubMed] [Google Scholar]
  20. Lanford R. E., Luckow V., Kennedy R. C., Dreesman G. R., Notvall L., Summers M. D. Expression and characterization of hepatitis B virus surface antigen polypeptides in insect cells with a baculovirus expression system. J Virol. 1989 Apr;63(4):1549–1557. doi: 10.1128/jvi.63.4.1549-1557.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Livingston D. M., Bradley M. K. The simian virus 40 large T antigen. A lot packed into a little. Mol Biol Med. 1987 Apr;4(2):63–80. [PubMed] [Google Scholar]
  22. Meinke W., Goldstein D. A., Smith R. A. Simian virus 40-related DNA sequences in a human brain tumor. Neurology. 1979 Dec;29(12):1590–1594. doi: 10.1212/wnl.29.12.1590. [DOI] [PubMed] [Google Scholar]
  23. Pan S., Abramczuk J., Knowles B. B. Immune control of SV40-induced tumors in mice. Int J Cancer. 1987 Jun 15;39(6):722–728. doi: 10.1002/ijc.2910390612. [DOI] [PubMed] [Google Scholar]
  24. Scherneck S., Rudolph M., Geissler E., Vogel F., Lübbe L., Wählte H., Nisch G., Weickmann F., Zimmermann W. Isolation of a SV40-like Papovavirus from a human glioblastoma. Int J Cancer. 1979 Nov 15;24(5):523–531. doi: 10.1002/ijc.2910240502. [DOI] [PubMed] [Google Scholar]
  25. Shearer M. H., Lanford R. L., Kennedy R. C. Monoclonal anti-idiotypic antibodies induce humoral immune responses specific for simian virus 40 large tumor antigen in mice. J Immunol. 1990 Aug 1;145(3):932–939. [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Takemoto K. K., Rabson A. S., Mullarkey M. F., Blaese R. M., Garon C. F., Nelson D. Isolation of papovavirus from brain tumor and urine of a patient with Wiskott-Aldrich syndrome. J Natl Cancer Inst. 1974 Nov;53(5):1205–1207. doi: 10.1093/jnci/53.5.1205. [DOI] [PubMed] [Google Scholar]
  29. Tevethia S. S., Blasecki J. W., Waneck G., Goldstein A. L. Requirement of thymus-derived theta-positive lymphocytes for rejection of DNA virus (SV 40) tumors in mice. J Immunol. 1974 Nov;113(5):1417–1423. [PubMed] [Google Scholar]
  30. Tevethia S. S., Flyer D. C., Tjian R. Biology of simian virus 40 (SV40) transplantation antigen (TrAg). VI. Mechanism of induction of SV40 transplantation immunity in mice by purified SV40 T antigen (D2 protein). Virology. 1980 Nov;107(1):13–23. doi: 10.1016/0042-6822(80)90268-8. [DOI] [PubMed] [Google Scholar]
  31. Yokota J., Akiyama T., Fung Y. K., Benedict W. F., Namba Y., Hanaoka M., Wada M., Terasaki T., Shimosato Y., Sugimura T. Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung. Oncogene. 1988 Oct;3(4):471–475. [PubMed] [Google Scholar]
  32. 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 Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES