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. 1987 Oct;84(19):6854–6858. doi: 10.1073/pnas.84.19.6854

Effective tumor immunotherapy directed against an oncogene-encoded product using a vaccinia virus vector.

R Bernards 1, A Destree 1, S McKenzie 1, E Gordon 1, R A Weinberg 1, D Panicali 1
PMCID: PMC299183  PMID: 3477812

Abstract

We have constructed a vaccinia virus recombinant that expresses the extracellular domain of the rat neu oncogene-encoded protein, a 185-kDa transmembrane glycoprotein termed p185. Strain NFS mice immunized with this recombinant virus developed a strong antibody response against the neu oncogene product and were fully protected against subsequent tumor challenge with neu-transformed NIH 3T3 cells. No tumor immunoprotection was found when recombinant virus-immunized mice were challenged with Ha-ras-transformed NIH 3T3 cells. These data indicate that immunization with a single oncogene-encoded antigen can fully and specifically protect animals against tumor cells bearing this antigen.

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Selected References

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

  1. Bargmann C. I., Hung M. C., Weinberg R. A. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell. 1986 Jun 6;45(5):649–657. doi: 10.1016/0092-8674(86)90779-8. [DOI] [PubMed] [Google Scholar]
  2. Bargmann C. I., Hung M. C., Weinberg R. A. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986 Jan 16;319(6050):226–230. doi: 10.1038/319226a0. [DOI] [PubMed] [Google Scholar]
  3. Bennink J. R., Yewdell J. W., Smith G. L., Moller C., Moss B. Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells. Nature. 1984 Oct 11;311(5986):578–579. doi: 10.1038/311578a0. [DOI] [PubMed] [Google Scholar]
  4. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  5. Chakrabarti S., Robert-Guroff M., Wong-Staal F., Gallo R. C., Moss B. Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature. 1986 Apr 10;320(6062):535–537. doi: 10.1038/320535a0. [DOI] [PubMed] [Google Scholar]
  6. Dente L., Cesareni G., Cortese R. pEMBL: a new family of single stranded plasmids. Nucleic Acids Res. 1983 Mar 25;11(6):1645–1655. doi: 10.1093/nar/11.6.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Drebin J. A., Link V. C., Stern D. F., Weinberg R. A., Greene M. I. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell. 1985 Jul;41(3):697–706. doi: 10.1016/s0092-8674(85)80050-7. [DOI] [PubMed] [Google Scholar]
  8. Drebin J. A., Link V. C., Weinberg R. A., Greene M. I. Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9129–9133. doi: 10.1073/pnas.83.23.9129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drebin J. A., Stern D. F., Link V. C., Weinberg R. A., Greene M. I. Monoclonal antibodies identify a cell-surface antigen associated with an activated cellular oncogene. Nature. 1984 Dec 6;312(5994):545–548. doi: 10.1038/312545a0. [DOI] [PubMed] [Google Scholar]
  10. Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science. 1986 Nov 7;234(4777):728–731. doi: 10.1126/science.3490689. [DOI] [PubMed] [Google Scholar]
  11. Hearing V. J., Gersten D. M., Montague P. M., Vieira W. D., Galetto G., Law L. W. Murine melanoma-specific tumor rejection activity elicited by a purified, melanoma-associated antigen. J Immunol. 1986 Jul 1;137(1):379–384. [PubMed] [Google Scholar]
  12. Hung M. C., Schechter A. L., Chevray P. Y., Stern D. F., Weinberg R. A. Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. Proc Natl Acad Sci U S A. 1986 Jan;83(2):261–264. doi: 10.1073/pnas.83.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kieny M. P., Lathe R., Drillien R., Spehner D., Skory S., Schmitt D., Wiktor T., Koprowski H., Lecocq J. P. Expression of rabies virus glycoprotein from a recombinant vaccinia virus. Nature. 1984 Nov 8;312(5990):163–166. doi: 10.1038/312163a0. [DOI] [PubMed] [Google Scholar]
  14. Lathe R., Kieny M. P., Gerlinger P., Clertant P., Guizani I., Cuzin F., Chambon P. Tumour prevention and rejection with recombinant vaccinia. 1987 Apr 30-May 6Nature. 326(6116):878–880. doi: 10.1038/326878a0. [DOI] [PubMed] [Google Scholar]
  15. Padhy L. C., Shih C., Cowing D., Finkelstein R., Weinberg R. A. Identification of a phosphoprotein specifically induced by the transforming DNA of rat neuroblastomas. Cell. 1982 Apr;28(4):865–871. doi: 10.1016/0092-8674(82)90065-4. [DOI] [PubMed] [Google Scholar]
  16. Panicali D., Davis S. W., Mercer S. R., Paoletti E. Two major DNA variants present in serially propagated stocks of the WR strain of vaccinia virus. J Virol. 1981 Mar;37(3):1000–1010. doi: 10.1128/jvi.37.3.1000-1010.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Panicali D., Davis S. W., Weinberg R. L., Paoletti E. Construction of live vaccines by using genetically engineered poxviruses: biological activity of recombinant vaccinia virus expressing influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5364–5368. doi: 10.1073/pnas.80.17.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Panicali D., Grzelecki A., Huang C. Vaccinia virus vectors utilizing the beta-galactosidase assay for rapid selection of recombinant viruses and measurement of gene expression. Gene. 1986;47(2-3):193–199. doi: 10.1016/0378-1119(86)90063-6. [DOI] [PubMed] [Google Scholar]
  19. Panicali D., Paoletti E. Construction of poxviruses as cloning vectors: insertion of the thymidine kinase gene from herpes simplex virus into the DNA of infectious vaccinia virus. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4927–4931. doi: 10.1073/pnas.79.16.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schechter A. L., Hung M. C., Vaidyanathan L., Weinberg R. A., Yang-Feng T. L., Francke U., Ullrich A., Coussens L. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985 Sep 6;229(4717):976–978. doi: 10.1126/science.2992090. [DOI] [PubMed] [Google Scholar]
  21. Schubert D., Heinemann S., Carlisle W., Tarikas H., Kimes B., Patrick J., Steinbach J. H., Culp W., Brandt B. L. Clonal cell lines from the rat central nervous system. Nature. 1974 May 17;249(454):224–227. doi: 10.1038/249224a0. [DOI] [PubMed] [Google Scholar]
  22. Shih C., Padhy L. C., Murray M., Weinberg R. A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981 Mar 19;290(5803):261–264. doi: 10.1038/290261a0. [DOI] [PubMed] [Google Scholar]
  23. Smith G. L., Mackett M., Moss B. Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen. Nature. 1983 Apr 7;302(5908):490–495. doi: 10.1038/302490a0. [DOI] [PubMed] [Google Scholar]

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