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Induction of P815 tumor immunity by recombinant Semliki Forest virus expressing the P1A gene

Abstract

The methylcholantrene-induced P815 mastocytoma tumor is derived from DBA/2 mice and expresses a weak tumor rejection antigen, P815A. The P1A gene, which encodes for the P815A antigen, is silent in most normal tissues with the exception of testis and placenta. These characteristics make P815 an interesting mouse model for the human MAGE-type tumor antigens. Recombinant Semliki Forest virus particles (rSFV) were constructed that expressed variants of the P815 antigen. Such particles, when used for vaccination, express the antigen only transiently since the viral vector is incapable of productive replication. Nevertheless, mice vaccinated with rSFV generated strong CTL responses and were protected against P815 tumor challenge.

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References

  1. Fernandez N et al. Active specific T-cell-based immunotherapy for cancer: nucleic acids, peptides, whole native proteins, recombinant viruses, with dendritic cell adjuvants or whole tumor cell-based vaccines. Principles and future prospects Cytokin Cell Molec Ther 1998 4: 53–65

    CAS  Google Scholar 

  2. Pardoll DM . Cancer vaccines Nature Med 1998 4: 525–531

    Article  CAS  PubMed  Google Scholar 

  3. Rosenberg SA et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma (see comments) Nature Med 1998 4: 321–327

    Article  CAS  PubMed  Google Scholar 

  4. Nestle FO et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells (see comments) Nature Med 1998 4: 328–332

    Article  CAS  PubMed  Google Scholar 

  5. Staveley OCK et al. Induction of antigen-specific T cell anergy: an early event in the course of tumor progression Proc Natl Acad Sci USA 1998 95: 1178–1183

    Article  Google Scholar 

  6. Germain RN . MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation Cell 1994 76: 287–299

    Article  CAS  PubMed  Google Scholar 

  7. Ostrand-Rosenberg S . Tumor immunotherapy: the tumor cell as an antigen-presenting cell Curr Opin Immunol 1994 6: 722–727

    Article  CAS  PubMed  Google Scholar 

  8. Jaffee EM, Pardoll DM . Considerations for the clinical development of cytokine gene-transduced tumor cell vaccines Methods 1997 12: 143–153

    Article  CAS  PubMed  Google Scholar 

  9. Arienti F et al. Limited antitumor T cell response in melanoma patients vaccinated with interleukin-2 gene-transduced allogeneic melanoma cells Hum Gene Ther 1996 7: 1955–1963

    Article  CAS  PubMed  Google Scholar 

  10. Simons JW et al. Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte–macrophage colony-stimulating factor gene transfer Cancer Res 1997 57: 1537–1546

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Van den Eynde BJ, van der Bruggen P . T cell defined tumor antigens Curr Opin Immunol 1997 9: 684–693

    Article  CAS  PubMed  Google Scholar 

  12. Van den Eynde B et al. The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice J Exp Med 1991 173: 1373–1384

    Article  CAS  PubMed  Google Scholar 

  13. Amar-Costesec A et al. Identification and characterization of the tumor-specific P1A gene product Biol Cell 1994 81: 195–203

    Article  CAS  PubMed  Google Scholar 

  14. Lethe B et al. Mouse tumor rejection antigens P815A and P815B: two epitopes carried by a single peptide Eur J Immunol 1992 22: 2283–2288

    Article  CAS  PubMed  Google Scholar 

  15. van der Bruggen P et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma Science 1991 254: 1643–1647

    Article  CAS  PubMed  Google Scholar 

  16. Van Pel A et al. Genes coding for tumor antigens recognized by cytolytic T lymphocytes Immunol Rev 1995 145: 229–250

    Article  CAS  PubMed  Google Scholar 

  17. Uyttenhove C et al. The expression of mouse gene P1A in testis does not prevent safe induction of cytolytic T cells against a P1A-encoded tumor antigen Int J Cancer 1997 70: 349–356

    Article  CAS  PubMed  Google Scholar 

  18. Warnier G et al. Induction of a cytolytic T-cell response in mice with a recombinant adenovirus coding for tumor antigen P815A Int J Cancer 1996 67: 303–310

    Article  CAS  PubMed  Google Scholar 

  19. Rosato A et al. CTL response and protection against P815 tumor challenge in mice immunized with DNA expressing the tumor-specific antigen P815A Hum Gene Ther 1997 8: 1451–1458

    Article  CAS  PubMed  Google Scholar 

  20. Davis NL, Brown KW, Johnston RE . A viral vaccine vector that expresses foreign genes in lymph nodes and protects against mucosal challenge J Virol 1996 70: 3781–3787

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Pugachev KV, Mason PW, Shope RE, Frey TK . Double-subgenomic Sindbis virus recombinants expressing immunogenic proteins of Japanese encephalitis virus induce significant protection in mice against lethal JEV infection Virology 1995 212: 587–594

    Article  CAS  PubMed  Google Scholar 

  22. Zhou X et al. Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus Proc Natl Acad Sci USA 1995 92: 3009–3013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Berglund P et al. Enhancing immune responses using suicidal DNA vaccines (see comments) Nature Biotechnol 1998 16: 562–565

    Article  CAS  Google Scholar 

  24. Berglund P, Fleeton MN, Smerdou C, Liljeström P . Immunization with recombinant Semliki Forest virus induces protection against influenza challenge in mice Vaccine 1998 17: 508–518

    Google Scholar 

  25. Liljeström P, Garoff H . A new generation of animal cell expression vectors based on the Semliki Forest virus replicon Nature Biotechnol 1991 9: 1356–1361

    Article  Google Scholar 

  26. Berglund P et al. Semliki Forest virus expression system: production of conditionally infectious recombinant particles Bio/Technology 1993 11: 916–920

    CAS  Google Scholar 

  27. Berglund P et al. Outcome of immunization of cynomolgus monkeys with recombinant Semliki Forest virus encoding human immunodeficiency virus type 1 envelope protein and challenge with a high dose of SHIV-4 virus AIDS Res Hum Retrovir 1997 13: 1487–1495

    Article  CAS  PubMed  Google Scholar 

  28. Mossman SP et al. Protection against lethal simian immunodeficiency virus SIVsmmPBj14 disease by a recombinant Semliki Forest virus gp160 vaccine and by a gp120 subunit vaccine J Virol 1996 70: 1953–1960

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Fleeton MN et al. Recombinant Semliki Forest virus particles encoding the prME or NS1 proteins of louping ill virus protect mice from lethal challenge J Gen Virol 1999 80: 1189–1198

    Article  CAS  PubMed  Google Scholar 

  30. Brichard VG et al. Individual differences in the orientation of the cytolytic T cell response against mouse tumor P815 Eur J Immunol 1995 25: 664–671

    Article  CAS  PubMed  Google Scholar 

  31. Grohmann U et al. CD8+ cell activation to a major mastocytoma rejection antigen, P815AB: requirement for tumor helper peptides in priming for skin test reactivity to a P815AB-relatedpeptide Eur J Immunol 1995 25: 2797–2802

    Article  CAS  PubMed  Google Scholar 

  32. Bour H et al. Differential requirement for CD4 help in the development of an antigen-specific CD8+ T cell response depending on the route of immunization J Immunol 1998 160: 5522–5529

    CAS  PubMed  Google Scholar 

  33. Fallarino F, Uyttenhove C, Boon T, Gajewski TF . Endogenous IL-12 is necessary for rejection of P815 tumor variants in vivo J Immunol 1996 156: 1095–1100

    CAS  PubMed  Google Scholar 

  34. Uyttenhove C, Van Snick J, Boon T . Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. I. Rejection by syngeneic mice J Exp Med 1980 152: 1175–1183

    Article  CAS  PubMed  Google Scholar 

  35. Uyttenhove C, Maryanski J, Boon T . Escape of mouse mastocytoma P815 after nearly complete rejection is due to antigen-loss variants rather than immunosuppression J Exp Med 1983 157: 1040–1052

    Article  CAS  PubMed  Google Scholar 

  36. Pross HF, Eidinger D . Antigenic competition: a review of nonspecific antigen-induced suppression Adv Immunol 1974 18: 133–168

    Article  CAS  PubMed  Google Scholar 

  37. Heufler C et al. Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells Eur J Immunol 1996 26: 659–668

    Article  CAS  PubMed  Google Scholar 

  38. Grohmann U et al. Dendritic cells, interleukin 12, and CD4+ lymphocytes in the initiation of class I-restricted reactivity to a tumor/self peptide Crit Rev Immunol 1998 18: 87–98

    Article  CAS  PubMed  Google Scholar 

  39. Glasgow GM, McGee MM, Sheahan BJ, Atkins GJ . Death mechanisms in cultured cells infected by Semliki Forest virus J Gen Virol 1997 78: 1559–1563

    Article  CAS  PubMed  Google Scholar 

  40. Carbone FR et al. Cross-presentation: a general mechanism for CTL immunity and tolerance Immunol Today 1998 19: 368–373

    Article  CAS  PubMed  Google Scholar 

  41. Boyle JS, Koniaras C, Lew AM . Influence of cellular location of expressed antigen on the efficacy of DNA vaccination: cytotoxic T lymphocyte and antibody responses are suboptimal when antigen is cytoplasmic after intramuscular DNA immunization Int Immunol 1997 9: 1897–1906

    Article  CAS  PubMed  Google Scholar 

  42. Inchauspe G et al. Plasmid DNA expressing a secreted or a nonsecreted form of hepatitis C virus nucleocapsid: comparative studies of antibody and T-helper responses following genetic immunization DNA Cell Biol 1997 16: 185–195

    Article  CAS  PubMed  Google Scholar 

  43. Kjerrulf M, Lowenadler B, Svanholm C, Lycke N . Tandem repeats of T helper epitopes enhance immunogenicity of fusion proteins by promoting processing and presentation Molec Immunol 1997 34: 599–608

    Article  CAS  Google Scholar 

  44. Lowenadler B et al. T and B cell responses to chimeric proteins containing heterologous T helper epitopes inserted at different positions Molec Immunol 1992 29: 1185–1190

    Article  CAS  Google Scholar 

  45. Aichele P et al. T cell priming versus T cell tolerance induced by synthetic peptides J Exp Med 1995 182: 261–266

    Article  CAS  PubMed  Google Scholar 

  46. Toes RE et al. Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction Proc Natl Acad Sci USA 1996 93: 7855–7860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Restifo NP . The new vaccines: building viruses that elicit antitumor immunity Curr Opin Immunol 1996 8: 658–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jones L, Ristow S, Yilma T, Moss B . Accidental human vaccination with vaccinia virus expressing nucleoprotein gene (letter) Nature 1986 319: 543

    Article  CAS  PubMed  Google Scholar 

  49. Rooney JF et al. Immunization with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and effect of revaccination J Virol 1988 62: 1530–1534

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Kundig TM, Kalberer CP, Hengartner H, Zinkernagel RM . Vaccination with two different vaccinia recombinant viruses: long-term inhibition of secondary vaccination Vaccine 1993 11: 1154–1158

    Article  CAS  PubMed  Google Scholar 

  51. Yang Y et al. Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo Gene Therapy 1996 3: 137–144

    PubMed  Google Scholar 

  52. Sjoberg EM, Suomalainen M, Garoff H . A significantly improved Semliki Forest virus expression system based on translation enhancer segments from the viral capsid gene Bio/Technology 1994 12: 1127–1131

    Article  CAS  Google Scholar 

  53. Salminen A et al. Membrane fusion process of Semliki Forest virus. II: Cleavage-dependent reorganization of the spike protein complex controls virus entry J Cell Biol 1992 116: 349–357

    Article  CAS  PubMed  Google Scholar 

  54. Liljeström P, Garoff H . Expression of proteins using Semliki Forest virus vectors. In: Ausubel FM et al (eds). Current Protocols in Molecular Biology Greene Publishing Associates and Wiley Interscience: New York 1994 16.20.1–16.20.16

    Google Scholar 

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Acknowledgements

We thank Dr Aline Van Pel and Dr Pierre Coulie (Ludwig Institute for Cancer Research, Brussels), for generous contribution of materials and helpful discussions. This work was supported by the Swedish Cancer Research Foundation to MJ and PL and by the Swedish Medical Research Council, the Swedish Council for Engineering Sciences, and the European Union Biotechnology Program to PL.

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Colmenero, P., Liljeström, P. & Jondal, M. Induction of P815 tumor immunity by recombinant Semliki Forest virus expressing the P1A gene. Gene Ther 6, 1728–1733 (1999). https://doi.org/10.1038/sj.gt.3301004

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