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Gene Therapy of Cancer pp 3–26Cite as

Immunizing Potential of Cytokine-Transduced Tumor Cells

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Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 35))

Abstract

The molecular definition of tumor antigens, costimulatory signals, and the possibility to genetically engineer tumor cells as well as simple protocols for efficient isolation and preparation of dendritic cells (DC) renew the interest in tumor immunotherapy and vaccination, in particular. Engineering of tumor cells with the gene of a particular cytokine is a way of releasing that cytokine at the tumor site. In contrast to bolus administration, it provides a constant supply of cytokine. If live-engineered tumor cells are injected, their proliferation results in both the provision of antigen and an increase of cytokine concentration until a physiological or a pharmacological threshold is reached, and its biological activity begins. The following inflammatory reaction is then responsible for tumor destruction, thus, turning off the initial trigger. The efficacy of this feedback action is determined by the type of cytokine, its quantity and activity, the histotype of the tumor and the molecules it releases, and its extracellular matrix (1). However, the relevant point is that a cascade of events other than tumor debulking are initiated by the transduced cytokines. Infiltration of different leukocyte types, including antigen-presenting cells (APC), and the release of secondary cytokines contribute to the induction of a systemic and memory response. Also, injection of replication in competent cells because of irradiation can exert the same effect, in this case the amount of cytokine to be released in situ to trigger the system, should be predetermined.

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References

  1. Colombo, M. P., Modesti A., Parmiani G., and Forni G. (1992) Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T-lymphocyte cross-talk. Cancer Res. 52, 4853–4857.

    PubMed  CAS  Google Scholar 

  2. Colombo, M. P. and Forni, G. (1994) Cytokine gene transfer in tumour inhibition and tentative tumour therapy: where are we now? Immunol. Today 15, 48–50.

    Article  PubMed  CAS  Google Scholar 

  3. Paglia, P., Chiodoni, C., Rodolfo, M., and Colombo, M. P. (1996) Murine dendritic cells loaded in vitro with soluble protein prime CTL against tumor antigen in vivo. J. Exp. Med. 183, 317–322.

    Article  PubMed  CAS  Google Scholar 

  4. Porgador, A., Snyder, D., and Gilboa, E. (1996) Induction of antitumor immunity using bone marrow-generated dendritic cells. J. Immunol. 156, 2918–2926.

    PubMed  CAS  Google Scholar 

  5. Huang, Y. C., Golumbeck, P., Ahmadzadeh, M., Jaffee, E., Pardoll, D., and Levitsky, H. (1994) Role of bone-marrow derived cells in presenting MHC class I-restricted tumor antigens. Science (Wash., DC) 264, 961–965.

    Article  CAS  Google Scholar 

  6. Bevan, M. J. (1976) Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J. Exp. Med. 143, 1283–1289.

    Article  PubMed  CAS  Google Scholar 

  7. Singh, S., Ross, S. R., Acena, M., Rowley, D. A., and Schreiber, H. (1992) Stroma is critical for preventing or permitting immunological destruction of antigenic cancer cells. J. Exp. Med. 175, 139–146.

    Article  PubMed  CAS  Google Scholar 

  8. Stoppacciaro, A., Melani, C., Parenza, M., Mastracchio, A., Bassi, C., Baroni, C., et al. (1993) Regression of an established tumor genetically modified to release G-CSF requires granulocyte-T cell cooperation and T cell-produced IFNγ. J. Exp. Med. 178, 151–161.

    Article  PubMed  CAS  Google Scholar 

  9. Pedrizet, G. A., Ross, S. R., Stauss, H. J., Singh, S., Koeppen, H., and Schreiber, H. (1990) Animals bearing malignant grafts reject normal grafts that express through gene transfer the same antigen. J. Exp. Med. 171, 1205–1220.

    Article  Google Scholar 

  10. Martinotti, A., Stoppacciaro, A., Vagliani, M., Melani, C., Spreafico, F., Wysocka, M., et al. (1995) CD4 T cells inhibits in vivo the CD8-mediated immune response against murine colon carcinoma cells transduced with IL-12 genes. Eur. J. Immunol. 25, 137–146.

    Article  PubMed  CAS  Google Scholar 

  11. Boon, T., Cerottini, J. C., Van den Eynde, B., Van der Bruggen, P., and van Pel, A. (1994) Tumor antigens recognized by T lymphocytes. Annu. Rev. Immunol. 12, 337–358.

    Article  PubMed  CAS  Google Scholar 

  12. Mandelboim, O., Bar-Haim, E., Vadai, E., Fridkin, M., and Eisenbach, L. (1997) Identification of shared tumor-associated antigen peptides between two spontaneous lung carcinomas J. Immunol. 159, 6030–6036.

    PubMed  CAS  Google Scholar 

  13. Peace, D. J., Smith, J. W., Chen, W., You, S. G., Cosand, W. L., Blake, J., and Cheever, M. A. (1994) Lysis of Ras oncogene-transformed cells by specific cytotoxic T lymphocytes elicited by primary in vitro immunization with mutated Ras peptides. J. Exp. Med. 179, 473–479.

    Article  PubMed  CAS  Google Scholar 

  14. Bronte, V., Tsung, K., Rao, J. B., Chen, P. W., Wang, M., Rosenberg, S. A., and Restifo, N. P. (1995) IL-2 enhances the function of recombinant poxvirus-based vaccines in the treatment of established pulmonary metastases. J. Immunol. 154, 5282–5289.

    PubMed  CAS  Google Scholar 

  15. Russel, W. M. S. and Burch, R. L. (1959) The Principles of Humane Experimental Technique. Methuen, London.

    Google Scholar 

  16. van Zutphen, L. F. M., Baumans, V., and Beynen, A. C. (1993) Principles of Laboratory Animal Science. Amsterdam, Elsevier.

    Google Scholar 

  17. Tuffery, A. A. (1987) Laboratory Animals: An Introduction for New Experimenters. Wiley, Chichester, England.

    Google Scholar 

  18. Donovan, J. and Brown, P. (1995) Care and handling of the laboratory animals, in Current Protocols in Immunology, Wiley, England, pp. 1.0.1–1.10.11.

    Google Scholar 

  19. Geran, R. I., Greenberg, N. H., Macdonald, M. M., Shumacher, A. M, and Abbot, B. J. (1972) Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother. Rep. 3, 1–88.

    Google Scholar 

  20. Allione, A., Consalvo, M., Nanni, P., Lollini, P. L., Cavallo, F., Giovarelli, M., et al. (1994) Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-10, TNFα, GM-CSF, and y-IFN gene or admixed with conventional adjuvants. Cancer Res. 54, 6022–6026.

    PubMed  CAS  Google Scholar 

  21. Rodolfo, M., Zilocchi, C., Melani, C., Cappetti, B., Arioli, I., Parmiani, G., and Colombo, M. P. (1996) Immunotherapy of experimental metastases by vaccination with interleukin gene-transduced adenocarcinoma cells sharing tumor-associated antigens. Comparison between IL-12 and IL-2 gene-transduced tumor cell vaccines. J. Immunol. 157, 5536–5542.

    PubMed  CAS  Google Scholar 

  22. Kopper, L., Van Hanh, K., and Lapis, K. (1982) Experimental model for liver metastasis formation using Lewis Lung Tumor J. Cancer Res. Clin. Oncol. 103, 31–38.

    Article  PubMed  CAS  Google Scholar 

  23. Saito, S., Bannerji, R., Gansbacher, B., Rosenthal, F. M., Romanenko, P., Heston, W. D., et al. (1994) Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines. Cancer Res. 54, 3516–3520.

    PubMed  CAS  Google Scholar 

  24. Vieweg, J., Heston, W. D., Gilboa, E., and Fair, W. R. (1994) An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer. Prostate 24, 291–298.

    Article  PubMed  CAS  Google Scholar 

  25. Ashley, D. M., Faiola, B., Nair, S., Hale, L. P., Bigner, D. D., and Gilboa, E. (1997) Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors. J. Exp. Med. 186, 1177–1182.

    Article  PubMed  CAS  Google Scholar 

  26. Salup, R. R., Herberman, R. B., and Wiltrout, R. H., (1985) Role of natural killer activity in development of spontaneous metastases in murine renal cancer. J. Urology 134, 1236–1241.

    CAS  Google Scholar 

  27. Wexler, H. (1966) Accurate identification of experimental pulmonary metastase J. Natl. Cancer Inst. 36, 641–643.

    PubMed  CAS  Google Scholar 

  28. Cobbold, S. P., Jayasurija, A., Nash, A., Prospero, T. D., and Waldmann, H. (1984) Therapy with monoclonal antibodies by elimination of T cell subsets. Nature 312, 548–551.

    Article  PubMed  CAS  Google Scholar 

  29. Herold, K. C., Montag, A. G., and Fitch, F. W. (1987) Treatment with anti-T-lymphocyte antibodies prevents induction of insulitis in mice given multiple doses of streptozocin. Diabetes 36, 796–801.

    Article  PubMed  CAS  Google Scholar 

  30. Kruisbeek, A. D. In vivo assays for mouse lymphocyte function, in Current Protocols in Immunology, Wiley, England, pp. 4.1.1-4.1.4..

    Google Scholar 

  31. Brunner, K. T., Mauel, J., Cerottini, J. C., and Chapuis, B. (1968) Quantitative assay of the lytic action of immune lymphoid cells on 51Cr labeled allogenic target cells in vitro: inhibition by isoantibody and by drugs. Immunology 14, 181–196.

    PubMed  CAS  Google Scholar 

  32. Langhorne, J. and Fisher Lindahl, K. (1981) Limiting dilution analysis of precursors of cytotoxic T lymphocytes, in Immunological Methods vol. 2 (Lefkovits, I. and Pernis, B., eds.), Academic, New York, pp. 221–231.

    Google Scholar 

  33. Lefkovits, I. and Waldmann, H. (1979) Limiting Dilution Analysis of Cells in the Immune System, Cambridge University Press, England.

    Google Scholar 

  34. Mac Donald, H. R., Cerottini, J. C., Ryser, J. E., Maryanski, J. L., Tarswell, C., Widmer, M. B., and Brunner, T. K. (1980) Quantitation and cloning of cytolytic T lymphocytes and their precursors Immunological Rev. 51, 93–150.

    Article  CAS  Google Scholar 

  35. Sharrock, C. E. M, Kaminski, E. M, and Man, S. (1990) Limiting dilution analysis of human T cells: a useful clinical tool. Immunol. Today 11, 281–285.

    Article  PubMed  CAS  Google Scholar 

  36. Taswell, C. (1981) Limiting dilution assays for the detrmination of immuno-competent cell frequencies. I. Data analysis. J. Immunol. 126, 1614–1619.

    PubMed  CAS  Google Scholar 

  37. Musiani, P., Modesti, A., Giovarelli, M., Cavallo, F., Colombo, M. P., Lollini, P. L., and Forni, G. (1997). Cytokines, tumor-cell death and immunogenicity: a question of choice. Immunol. Today 18, 32–36.

    Article  PubMed  CAS  Google Scholar 

  38. Pericle F., Giovarelli, M., Colombo, M. P., Ferrari, G., Musiani, P., Modesti, A., et al. (1994) An efficient Th2-type memory follows CD8+lymphocyte-driven and eosinophil-mediated rejection of a spontaneous mouse mammary adenocarcinoma engineered to produce IL-4. J. Immunol. 153, 5659–5668.

    PubMed  CAS  Google Scholar 

  39. Morton, D., Foshag, L. J., Hoon, D. S. B., Nizze, J. A., Wanek, L. A., Chang, C., et al. (1992) Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann. Surg. 216, 463–469.

    Article  PubMed  CAS  Google Scholar 

  40. Jager, E., Chen, Y., Drijfhout, M., Karbach, J., Ringhoffer, M., Jager, D., et al. (1998) Simultaneous humoral and cellular immune response against Cancer-Testis antigene NY-ESO-1: definition of human Histocompatibility Leukocyte antigen (HLA)-A2-binding peptide epitopes J. Exp. Med. 187, 265–270.

    Article  PubMed  CAS  Google Scholar 

  41. Hara, I., Takechi, Y., and Houghton, A. N. (1995) Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein. J. Exp. Med. 182, 1609–1614.

    Article  PubMed  CAS  Google Scholar 

  42. Bright, R. K., Shearer, M. H., and Kennedy R. C. (1994) Immunization of BALB/ c mice with recombinant Simian Virus 40 Large Tumor antigen induces antibody-dependent cell mediated cytotoxicity against Simian virus 40-transformed cells J. Immunol. 153, 2064–2071.

    PubMed  CAS  Google Scholar 

  43. Rodolfo, M., Bassi, C., Salvi, C., and Parmiani, G. (1991) Therapeutic use of along-term cytotoxic T cell line recognizing a common tumour-associated antigen: the pattern of in vitro reactivity predicts the in vivo effect on different tumours. Cancer Immunol. Immunother. 34, 53–57.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Experimental Oncology Department, Istituto Nazionale Tumori, Milano, Italy

    Mario P. Colombo

  2. Department of Experimental Oncology, Istituto Nazionale Tumori, Milano, Italy

    Monica Rodolfo

Authors
  1. Mario P. Colombo
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  2. Monica Rodolfo
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Editor information

Editors and Affiliations

  1. Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Wolfgang Walther  & Ulrike Stein  & 

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© 2000 Humana Press Inc., Totowa, NJ

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Colombo, M.P., Rodolfo, M. (2000). Immunizing Potential of Cytokine-Transduced Tumor Cells. In: Walther, W., Stein, U. (eds) Gene Therapy of Cancer. Methods in Molecular Medicine™, vol 35. Humana Press. https://doi.org/10.1385/1-59259-086-1:3

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  • DOI: https://doi.org/10.1385/1-59259-086-1:3

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-714-4

  • Online ISBN: 978-1-59259-086-5

  • eBook Packages: Springer Protocols

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