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Experimental Basis for Immunotherapy of Metastases

  • V. Schirrmacher
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)

Abstract

Novel biological strategies have emerged in recent years for the treatment of cancer. These include transfer of hematopoietic stem cells for marrow reconstitution (BMT) after high-dose chemotherapy, transfer of activated tumor-reactive lymphocytes for adoptive cellular immunotherapy (ADI) of cancer and metastases, postoperative active specific immunization (ASI) with cancer vaccines, gene therapy, differentiation therapy, antisense therapy, immunotoxins or receptor-based therapies. Some biological treatments have already been established for certain forms of cancer, for instance interferon-α administration for Hairy cell leukemia, BCG (Bacillus Calmette Guérin) for superficial bladder carcinoma and allogeneic or autologous BMT for certain leukemic diseases. ADI was reported to have an overall response rate of about 25% in metastatic melanoma and renal cell carcinoma patients. For the vast majority of human cancer, however, such as carcinomas of lung, gastrointestinal tract, breast or prostate, no effective biological treatments have been found yet.

This report does not attempt to review the whole area of immunotherapy but focuses on progress from the author’s laboratory.

Keywords

Newcastle Disease Virus Recombinant Inbred Bispecific Antibody Autologous Tumor Cell Graft Versus Leukemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Schirrmacher V, Beckhove P,KrügerA, Rocha M, Umansky V, Fichtner K-P, Hull W, Zangemeister Wittke U, Griesbach A, Jurianz K, von Hoegen P (1995) Effective immune rejection of advanced metastasized cancer. Int J Oncol 6: 505–521PubMedGoogle Scholar
  2. 2.
    Roschenberg SA, Lotze MT, Yang JC, Topalian SL, Chang AE, Schwartzentruber D,Aebersold P, Leitman S, Linehan WM, Seipp CA, White DE, Steinberg SM (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Nat Cancer Inst 85: 622–632CrossRefGoogle Scholar
  3. 3.
    Osband ME, Lavin PT, Babayan RK, Graham S, Lamm DL, Parker B, Sawczyck I, Ross S, Krane RJ (1990) Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal cell carinoma. Lancet 335: 994–998PubMedCrossRefGoogle Scholar
  4. 4.
    Rocha M, Umansky V, Lee K, Hacker HJ, Benner A, Schirrmacher V (1997) Differences between graft-versus-leukemia (GvL) and graft-versus-host (GvH) reactivity. I. Interaction of donor immune T cells with tumor and/or host cells. Blood 6: 2189–2202Google Scholar
  5. 5.
    Lee K, Hacker H-J, Umansky V, Schirrmacher V, Rocha M (1996) Changes in liver glycogen and lipid metabolism during transient graft-versushost ( GvH) and graft-versus-leukemia GvL) reactivity. Int J Oncol 9: 635–643PubMedGoogle Scholar
  6. 6.
    Fichtner KP, Schirrmacher V, Griesbach A, Hull WE (1996) Characterization of a murine lymphoma cell line by 31P-NMR spectroscopy, in vivo monitoring of the local antitumor effects of systemic immune cell transfer. Int J Cancer 66: 484–495PubMedCrossRefGoogle Scholar
  7. 7.
    Schirrmacher V, Griesbach A, Gehring M, Lehr B (1996) Genetic separation of GvL and GvH reactivity in new recombinant-inbred tumor-resistant mouse strains. Int J Oncol 8: 1035–1044PubMedGoogle Scholar
  8. 8.
    Krüger A, Schirrmacher V, von Hoegen P (1994) Scattered micrometastasis visualized at the Single cell level: detection and re-isolation of lacZ labelled metastasized lymphoma cells. Int J Cancer 58: 275–284PubMedCrossRefGoogle Scholar
  9. 9.
    Rocha M, Kruger A, Van Rooij en N, Schirrmacher V, Umansky V (1995) Liver endothelial cells participate in T cell dependent host resistance to lymphoma metastasis by production f nitric oxide in vivo: Int J Cancer 63: 405–411Google Scholar
  10. 10.
    Umansky V, Rocha M, Krüger A, von Hoegen P, Schirrmacher V (1995) In situ activated macrophages are involved in host resistance to lymphoma metastasis by production of nitric oxide. Int J Oncol 7: 33–40PubMedGoogle Scholar
  11. 11.
    Heicappell R, Schirrmacher V, von Hoegen P, Ahiert T,Appelhans B (1986) Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. Int J Cancer 37: 569–577PubMedCrossRefGoogle Scholar
  12. 12.
    Plaksin D, Progedor A, Vadai E, Feldman M, Schirrmacher V, Eisenbach L (1994) Effective anti metastatic melanoma vaccination with tumor cells transfected with MHC genes and/or infected with Newcastle Disease Virus (NDV). Int J Cancer 59: 796–801PubMedCrossRefGoogle Scholar
  13. 13.
    Khazaie K, Prifti S, Beckhove P, Griesbach A, Russell S, Collins M, Schirrmacher V (1994) Persistence of dormant tumor-cells in the bone marrow of tumor-cell-vaccinated mice correlates with long-term immunological protection. Proc Nati Acad 91: 7430–7434CrossRefGoogle Scholar
  14. 14.
    Ertel C, Millar NS, Emmerson PT, Schirrmacher V, von Hoegen P (1993) Viral hemagglutinin augments peptide specific cytotoxic T-cell responses. Eur J Immunol 23: 2592–2596PubMedCrossRefGoogle Scholar
  15. 15.
    Haas C, Schirrmacher V (1996) Immunogenicity increase of autologous tumor cell vaccines by virus infection and attachment of bispecific antibodies. Cancer Immunol Immunother 43: 190–194PubMedCrossRefGoogle Scholar
  16. 16.
    Ahlert T, Sauerbrei W, Bastert G, Ruhland S, Bartik B, Simiantonaki N, Schumacher J, Häcker B, Schumacher M, Schirrmacher V (1997) Tumor cell number and viability as quality and efficacy parameters of autologous virus modified cancer vaccines. J Clin Oncol 15: 1354–1366PubMedGoogle Scholar
  17. 17.
    Schirrmacher V, von Hoegen P (1993) Importance of tumor cell membrane integrity and viability for CTL activation by cancer vaccines. Vaccine Research 2, No. 3: 183–196Google Scholar
  18. 18.
    Jurianz K, Haas C, Hubbe M, Ertel C, Brunner G, Altevogt P, Schirrmacher V, von Hoegen P (1995) Adhesive function of Newcastle Disease Virus hemagglutinin in tumor-host interaction. Int J Oncol 7: 539–545PubMedGoogle Scholar
  19. 19.
    Von Hoegen P, Zawatzky R, Schirrmacher V (1990) Modification of tumor cells by a low dose of Newcastle Disease Virus: III. Potentiation of tumor specific cytolytic T cell activity via induction of interferon, alfa, beta. Cellular Immunology 126: 80–90CrossRefGoogle Scholar
  20. 20.
    Schirrmacher V, Griesbach A, Zangemeister U (994) GGG-Irradiated viable tumor cells as whole cell vaccines can stimulate in situ syngeneic anti-tumor CTL and DTH reactivity while tumor cell lysates elicit only DTH reactivity. Vaccine Research 3, No. 1: 31–48Google Scholar
  21. 21.
    Schlag P, Manasterski M, Gerneth Th, Hohen-berger P, Dueck M, Herfarth Ch, Liebrich W, Schirrmacher V (1972) Active specific immunotherapy NDV modified autologous tumor cells following liver metastases resection in colorectal cancer: first evaluation of clinical response of a phase II trial. Cancer Immunol Immunother 35: 325–330CrossRefGoogle Scholar
  22. 22.
    Liebrich W, Schlag P, Manasterski M, Lehner B, Stîhr M, Miller P, Schirrmacher V (1991) In vitro and clinical characterization of a Newcastle Disease Virusmodified autologous tumor cell vaccine for treatment of colorectal cancer patients. Eur J Cancer 27: 703–710PubMedCrossRefGoogle Scholar
  23. 23.
    Ockert D, Schirrmacher V, Beck N, Stoelben E, Ahiert T, Flechtenmacher J, Hagmüller E, Nagel M, Saeger HD (1996) Newcastle disease virus in- fected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma. Clin Cancer Res 2: 21–28PubMedGoogle Scholar
  24. 24.
    Pomer S, Thile R, Daniel V, Wiemer R, Löhrke H, Schirrmacher V, Staehler G (1991) Sequential treatment of patients with advanced renal cell carcinoma with autologous tumor vaccine and subcutaneous administration of recombinant Interleukin-2 and Interferon-a-2b. World J Urol 9: 223–227CrossRefGoogle Scholar
  25. 25.
    Pomer S, Schirrmacher V, Thiele R, Löhrke H, Staehler G (1995) Tumor response and 4-year survival data of patients with advanced renal cell carcinoma treated with autologous tumor vaccine and subcutaneous r-IL-2 and IFN-Alpha 2b. Int J Oncol 6: 947–954PubMedGoogle Scholar
  26. 26.
    Möbus V, Horn S, Stoeck M, Schirrmacher V (1993) Tumor cell vaccination for gynecological tumors. Hybridoma 12: 543–547PubMedCrossRefGoogle Scholar
  27. 27.
    Patel BT, Lutz MB, Schlag P, Schirrmacher V (1992) An analysis of autologous T cell anti-tumor response in colon carcinoma patients following active specific immunisation (ASI). Int J Cancer 51: 878–885PubMedCrossRefGoogle Scholar
  28. 28.
    Stoeck M, Marland-Noske C, Manasterski M, Zawatzky R, Horn S, Möbus V, Schlag P, Schirrmacher V (1993) In vitro expansion and analysis of T lymphocyte microcultures obtained from the vaccination sites of cancer patients undergoing active specific immunization with autologous Newcastle-disease-virus-modified tumor cells. Cancer Immunol Immunother 37: 240–244PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • V. Schirrmacher
    • 1
  1. 1.Division of Cellular ImmunologyGerman Cancer Research CenterHeidelbergGermany

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