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Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

Gene Therapy volume 6, pages 1475–1481 (1999)Cite this article

A Corrigendum to this article was published on 16 November 1999

Abstract

Genetic modification of tumour cells with the GM-CSF encoding gene renders these cells more potent, as autologous tumour cell vaccine, than their wild-type counterparts. However, autologous vaccines are impractical for wide-scale clinical use and we have therefore investigated the efficacy of the GM-CSF genetic modification approach with an allogeneic whole cell tumour vaccine. In this report, we show that the allogeneic K1735-M2 (H-2k) melanoma cell vaccine induces a specific protective anti-tumour response against the syngeneic B16-F10 (H-2b) melanoma tumour in C57BL/6J mice. In vitro T cell work demonstrated that vaccination of animals with the allogeneic cell vaccine generated cytotoxic T cells specific for the autologous tumour. In vivo T cell subset depletion experiments also illustrated that this anti-tumour effect was mediated by both CD4+ve and CD8+ve T cells, suggesting that the allogeneic vaccine may operate through the ‘cross-priming’ phenomenon whereby tumour antigens are processed and presented to T cells by the host’s own antigen presenting cells (APC). Thus, we transduced K1735-M2 cells with a GM-CSF expressing retroviral vector and showed anti-tumour activity of the GM-CSF secreting K1735-M2 cells as a therapeutic vaccine against the syngeneic B16-F10 tumour. Our data imply that GM-CSF genetically modified allogeneic whole cell tumour vaccines could be successful in the clinic. In addition, more potent combination gene therapy strategies could be tested using this therapeutic allogeneic vaccine model.

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References

  1. Dranoff G et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte–macrophage colony-stimulating factor stimulates potent, specific, and long lasting anti-tumor immunity Proc Natl Acad Sci USA 1993 90: 3539–3543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Vieweg J et al. Immunotherapy of prostate cancer in the dunning rat model: use of cytokine gene modified tumor vaccines Cancer Res 1994 54: 1760–1765

    CAS  PubMed  Google Scholar 

  3. Dunussi-Joannopoulos K et al. Gene immunotherapy in murine acute myeloid more potent antitumour immunity compared with B7 family and other cytokine vaccines Blood 1998 91: 222–230

    CAS  PubMed  Google Scholar 

  4. 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 

  5. Huang AY et al. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens Science 1994 264: 961–965

    Article  CAS  PubMed  Google Scholar 

  6. Maass G et al. Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination Proc Natl Acad Sci USA 1995 92: 5540–5544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Schweighoffer T, Schmidt W, Buschle M, Birnstiel ML . Depletion of naive T cells of the peripheral lymph nodes abrogates systemic antitumour protection conferred by IL-2 secreting cancer vaccines Gene Therapy 1996 3: 819–824

    CAS  PubMed  Google Scholar 

  8. Souberbielle BE et al. Comparison of four strategies for tumour vaccination in the B16-F10 melanoma model Gene Therapy 1998 5: 1447–1454

    Article  CAS  PubMed  Google Scholar 

  9. Robbins PF, El-Gamil M, Kawakami Y, Rosenberg SA . Recognition of immunotherapy Cancer Res 1994 54: 3124–3126

    CAS  PubMed  Google Scholar 

  10. Brichard V et al. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas J Exp Med 1993 178: 489–495

    Article  CAS  PubMed  Google Scholar 

  11. 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 

  12. Dalgleish A . The case for therapeutic vaccines Melanoma Res 1996 6: 5–10

    Article  CAS  PubMed  Google Scholar 

  13. Ashley DM et al. A genetically modified allogeneic cellular vaccine generates MHC class I-restricted responses against tumor associated antigens and protects against CNS tumors in vivo J Neuroimmunol 1997 78: 34–46

    Article  CAS  PubMed  Google Scholar 

  14. Kim TS, Russell SJ, Collins MK, Cohen EP . Immunity to B16 melanoma in mice immunized with IL-2 secreting allogeneic mouse fibroblasts expressing melanoma associated antigens Int J Cancer 1992 51: 283–289

    Article  CAS  PubMed  Google Scholar 

  15. Kim TS, Russell SJ, Collins MK, Cohen EP . Immunization with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma associated antigens prolongs the survival of mice with melanoma Int J Cancer 1993 55: 865–872

    Article  CAS  PubMed  Google Scholar 

  16. Toes RE et al. Protective antitumour immunity induced by immunization with completely allogeneic tumour cells Cancer Res 1996 56: 3782–3787

    CAS  PubMed  Google Scholar 

  17. Kim YS, Slomski R, Cohen EP . Immunity to melanoma in mice immunized with transfected mouse fibroblasts expressing melanoma associated antigens Cancer Immunol Immunother 1991 34: 163–168

    Article  CAS  PubMed  Google Scholar 

  18. Knight BC et al. Allogeneic murine melanoma cell vaccine: a model for the development of human allogeneic cancer vaccine Melanoma Res 1996 6: 299–306

    Article  CAS  PubMed  Google Scholar 

  19. Morton DL et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine Ann Surg 1992 216: 465–470

    Article  Google Scholar 

  20. Arienti F et al. Limited antitumour 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 

  21. Bowman LC et al. Interleukin-2 gene modified allogeneic tumor cells for treatment of relapsed neuroblastoma Hum Gene Ther 1998 9: 835–843

    Article  Google Scholar 

  22. Thomas MC, Greten TF, Pardoll DM, Jaffee EM . Enhanced tumor protection by granulocyte–macrophage colony-stimulating factor expression at the site of an allogeneic vaccine Hum Gene Ther 1998 9: 835–843

    Article  CAS  PubMed  Google Scholar 

  23. Jaffee EM et al. A phase I clinical trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene for the treatment of pancreatic adenocarcinoma Hum Gene Ther 1998 9: 1951–1971

    Article  CAS  PubMed  Google Scholar 

  24. Inaba K et al. Identification of proliferating dendritic cell precursors in mouse blood J Exp Med 1992 175: 1157–1167

    Article  CAS  PubMed  Google Scholar 

  25. Bevan MJ . Antigen presentation to cytotoxic T lymphocytes in vivo J Exp Med 1995 182: 639–641

    Article  CAS  PubMed  Google Scholar 

  26. Hearing VJ . Murine melanoma-specific tumour rejection activity elicited by a purified, melanoma associated antigen J Immunol 1986 137: 379–384

    CAS  PubMed  Google Scholar 

  27. Bernhard H et al. Cellular immune responses to human renal cell carcinomas: definition of a common antigen recognized by HLA-A2-restricted cytotoxic T lymphocytes (CTL) clones Int J Cancer 1994 59: 807–842

    Article  Google Scholar 

  28. Weynants P . Expression of mage genes by non-small-cell lung carcinomas Int J Cancer 1994 56: 826–829

    Article  CAS  PubMed  Google Scholar 

  29. Aruga A, Aruga E, Chang AE . Reduced efficacy of allogeneic versus syngeneic fibroblasts modified to secrete cytokines as a tumour vaccine adjuvant Cancer Res 1997 57: 3230–3237

    CAS  PubMed  Google Scholar 

  30. Castleden SA et al. A family of bicistronic vectors to enhance both local and systemic antitumour effects of HSVtk or cytokine expression in a murine melanoma model Hum Gene Ther 1997 8: 2087–2102

    Article  CAS  PubMed  Google Scholar 

  31. Yu JS, Burwick JA, Dranoff G, Breakefield XO . Gene therapy for metastatic brain tumors by vaccination with granulocyte–macrophage colony-stimulating factor transduced tumor cells Hum Gene Ther 1997 8: 1065–1072

    Article  CAS  PubMed  Google Scholar 

  32. Parney IF et al. Granulocyte–macrophage colony-stimulating factor and B7–2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/Beige mouse–human glioblastoma multiforme model Hum Gene Ther 1997 8: 1073–1085

    Article  CAS  PubMed  Google Scholar 

  33. Hrouda D et al. Allogeneic whole tumour cell vaccination in the rat model of prostate cancer Cancer Res (submitted)

  34. Ben-Yosef R, Or R, Nagler A, Slavin S . Graft-versus-tumour and graft-versus-leukaemia effect in a patient with concurrent breast cancer and acute myelocytic leukaemia Lancet 1996 348: 1242–1243

    Article  CAS  PubMed  Google Scholar 

  35. Eibl B et al. Evidence for a graft-versus-tumour effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer Blood 1996 88: 1501–1508

    CAS  PubMed  Google Scholar 

  36. Fidler IJ . Biological behavior of malignant tumor cells correlated to their survival in vivo Cancer Res 1975 35: 218–224

    CAS  PubMed  Google Scholar 

  37. Kripke ML . Speculations on the role of ultraviolet radiation in the development of malignant melanoma J Natl Cancer Inst 1979 63: 541–545

    Article  CAS  PubMed  Google Scholar 

  38. Sugiura K, Stock CC . Studies in a tumour spectrum III: the effect of phosphoramides on the growth of a variety of mouse and rat tumours Cancer Res 1955 15: 38–51

    CAS  PubMed  Google Scholar 

  39. Cobbold SP et al. Therapy with monoclonal antibodies by elimination of T cell subsets in vivo Nature 1984 312: 548–551

    Article  CAS  PubMed  Google Scholar 

  40. Morgenstern JP, Land H . Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection and complimentary helper-free packaging cell line Nucleic Acids Res 1990 18: 3587–3596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to Dr D Bennet (St George’s Hospital Medical School, UK) and Professor IJ Fidler (MD Anderson Houston, TX, USA) for access to the B16-F10 and K1735-M2 cells lines, and to Professor F Farzaneh (King’s College School of Medicine and Dentistry, UK) for reading the manuscript.

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Authors and Affiliations

  1. Department of Oncology, St George’s Hospital Medical School, London, UK

    J Kayaga, T Scott-Taylor & A G Dalgleish

  2. Department of Molecular Medicine, King’s College School of Medicine and Dentistry, Rayne Institute, London, UK

    B E Souberbielle

  3. Department of Medicine, The Lung Unit, The Royal Marsden Hospital, Sutton, UK

    B E Souberbielle

  4. Department of Immunology, St Bartholomew’s Hospital and the Royal London School of Medicine and Dentistry, London, UK

    N Sheikh & W J W Morrow

  5. Imperial Cancer Research Fund Laboratory of Molecular Therapy, ICRF Oncology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK

    R Vile

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Kayaga, J., Souberbielle, B., Sheikh, N. et al. Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine. Gene Ther 6, 1475–1481 (1999). https://doi.org/10.1038/sj.gt.3300961

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