Skip to main content
SpringerLink
Log in

Dendritic Cells in Clinical Trials for Multiple Myeloma

  • Protocol
Adoptive Immunotherapy: Methods and Protocols

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 109))

  • 966 Accesses

Abstract

Due to the existence of the truly specific tumor antigen idiotype in multiple myeloma and based on encouraging data from dendritic cell vaccinated B-cell non-Hodgkin’s lymphoma (NHL) patients, dendritic cell-based vaccination was first initiated in myeloma patients in 1995. This overview will summarize published and ongoing clinical trials in patients with multiple myeloma who are treated with idiotype-based dendritic cell (Id/DC) vaccination. All groups of investigators have found that Id/DC vaccination of multiple-myeloma patients is feasible and that myeloma-specific immunity can be induced in heavily pretreated individuals. In future trials, new dendritic cell-based immunization strategies will be investigated based on techniques like RNA transfection of DC.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Attal, M., Harousseau, J. L., Stoppa, A. M., et al. (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N. Engl. J. Med. 335 91–97.

    Article  PubMed  CAS  Google Scholar 

  2. Child, J. A., Morgan, G. J., Davies, F. E., et al. (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N. Engl. J. Med. 348, 1875–1883.

    Article  PubMed  CAS  Google Scholar 

  3. Singhal, S., Mehta, J., Desikan, R., et al. (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 341, 1565–1571.

    Article  PubMed  CAS  Google Scholar 

  4. Richardson, P. (2003) Clinical update: proteasome inhibitors in hematologic malignancies. Cancer Treat. Rev. 29(Suppl. 1) 33–39.

    Article  PubMed  CAS  Google Scholar 

  5. Lynch, R. G., Graff, R. J., Sirisinha, S., Simms, E. S., and Eisen, H. N. (1972) Myeloma proteins as tumor-specific transplantation antigens. Proc. Natl. Acad. Sci. USA 69, 1540–1544.

    Article  PubMed  CAS  Google Scholar 

  6. Pellat-Deceunynck, C. (2003) Tumour-associated antigens in multiple myeloma. Br. J. Haematol. 120, 3–9.

    Article  PubMed  CAS  Google Scholar 

  7. van Baren, N., Brasseur, F., Godelaine, D., et al. (1999) Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood 94, 1156–1164.

    PubMed  Google Scholar 

  8. Brossart, P., Schneider, A., Dill, P., et al. (2001) The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. Cancer Res. 61, 6846–6850.

    PubMed  CAS  Google Scholar 

  9. Chiriva-Internati, M., Wang, Z., Salati, E., Bumm, K., Barlogie, B., and Lim, S. H. (2002) Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma. Blood 100, 961–965.

    Article  PubMed  CAS  Google Scholar 

  10. Tureci, O., Sahin, U., and Pfreundschuh, M. (1997) Serological analysis of human tumor antigens: molecular definition and implications. Mol. Med. Today 3, 342–349.

    Article  PubMed  CAS  Google Scholar 

  11. Kwak, L. W., Campbell, M. J., Czerwinski, D. K., Hart, S., Miller, R. A., and Levy, R. (1992) Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N. Engl. J. Med. 327, 1209–1215.

    Article  PubMed  CAS  Google Scholar 

  12. Hsu, F. J., Caspar, C. B., Czerwinski, D., et al. (1997) Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma-long-term results of a clinical trial. Blood 89, 3129–3135.

    PubMed  CAS  Google Scholar 

  13. Bendandi, M., Gocke, C. D., Kobrin, C. B., et al. (1999) Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat. Med. 5, 1171–1177.

    Article  PubMed  CAS  Google Scholar 

  14. Bergenbrant, S., Yi, Q., Osterborg, A., et al. (1996) Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients. Br. J. Haematol. 92, 840–846.

    Article  PubMed  CAS  Google Scholar 

  15. Osterborg, A., Yi, Q., Henriksson, L., et al. (1998) Idiotype immunization combined with granulocyte-macrophage colony-stimulating factor in myeloma patients induced type I, major histocompatibility complex-restricted, CD8-and CD4-specific T-cell responses. Blood 91, 2459–2466.

    PubMed  CAS  Google Scholar 

  16. Massaia, M., Borrione, P., Battaglio, et al. (1999) Idiotype vaccination in human myeloma: generation of tumor-specific immune responses after high-dose chemotherapy. Blood 94, 673–683.

    PubMed  CAS  Google Scholar 

  17. Reichardt, V. L., Okada, C. Y., Stockerl-Goldstein, K. E., Bogen, B., and Levy, R. (1997) Rationale for adjuvant idiotypic vaccination after high-dose therapy for multiple myeloma. Biol. Blood Marrow Transplant. 3, 157–163.

    PubMed  CAS  Google Scholar 

  18. Hsu, F. J., Benike, C., Fagnoni, F., et al. (1996) Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat. Med. 2, 52–58.

    Article  PubMed  CAS  Google Scholar 

  19. Timmerman, J. M., Czerwinski, D. K., Davis, T. A., et al. (2002) Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 99, 1517–1526.

    Article  PubMed  CAS  Google Scholar 

  20. Reichardt, V. L., Okada, C. Y., Liso, A., et al. (1999) Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma-a feasibility study. Blood 93, 2411–2419.

    PubMed  CAS  Google Scholar 

  21. Raje, N., Gong, J., Chauhan, D., et al. (1999) Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi’s sarcoma herpesvirus gene sequences. Blood 93, 1487–1495.

    PubMed  CAS  Google Scholar 

  22. Brown, R. D., Pope, B., Murray, A., et al. (2001) Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood 98, 2992–2998.

    Article  PubMed  CAS  Google Scholar 

  23. Ratta, M., Fagnoni, F., Curti, A., et al. (2002) Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100, 230–237.

    Article  PubMed  CAS  Google Scholar 

  24. Wen, Y. J., Ling, M., Bailey-Wood, R., and Lim, S. H. (1998) Idiotypic protein-pulsed adherent peripheral blood mononuclear cell-derived dendritic cells prime immune system in multiple myeloma. Clin. Cancer Res. 4,957–962.

    PubMed  CAS  Google Scholar 

  25. Ratta, M., Curti, A., Fogli, M., et al. (2000) Efficient presentation of tumor idiotype to autologous T cells by CD83(+) dendritic cells derived from highly purified circulating CD14(+) monocytes in multiple myeloma patients. Exp. Hematol. 28, 931–940.

    Article  PubMed  CAS  Google Scholar 

  26. Titzer, S., Christensen, O., Manzke, O., et al. (2000) Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects. Br. J. Haematol. 108,805–816.

    Article  PubMed  CAS  Google Scholar 

  27. Tarte, K., Lu, Z. Y., Fiol, G., Legouffe, E., Rossi, J. F., and Klein, B. (1997) Generation of virtually pure and potentially proliferating dendritic cells from non-CD34 apheresis cells from patients with multiple myeloma. Blood 90, 3482–3495.

    PubMed  CAS  Google Scholar 

  28. Butch, A. W., Kelly, K. A., and Munshi, N. C. (2001) Dendritic cells derived from multiple myeloma patients efficiently internalize different classes of myeloma protein. Exp. Hematol. 29, 85–92.

    Article  PubMed  CAS  Google Scholar 

  29. Tarte, K., Fiol, G., Rossi, J. F., and Klein, B. (2000) Extensive characterization of dendritic cells generated in serum-free conditions: regulation of soluble antigen uptake, apoptotic tumor cell phagocytosis, chemotaxis and T cell activation during maturation in vitro. Leukemia 14, 2182–2192.

    Article  PubMed  CAS  Google Scholar 

  30. Reichardt, V.L., Milazzo, C., Brugger, W., Einsele, H., Kanz, L, and Brossart, P. (2003) Idiotype vaccination of multiple myeloma patients using monocyte-derived dendritic cells. Haematologica 88,1139–1149.

    PubMed  Google Scholar 

  31. Reichardt, V., Okada, C., Benike, C., et al. (1996) Idiotypic vaccination using dendritic cells for multiple myeloma patients after autologous peripheral blood stem cell transplantation. Blood 88 (Suppl 1), 481a.

    Google Scholar 

  32. Liso, A., Stockerl-Goldstein, K. E., Auffermann-Gretzinger, S., et al. (2000). Idiotype vaccination using dendritic cells after autologous peripheral blood progenitor cell transplantation for multiple myeloma. Biol. Blood Marrow Transplant. 6, 621–627.

    Article  PubMed  CAS  Google Scholar 

  33. Lim, S. H. and Bailey-Wood, R. (1999) Idiotypic protein-pulsed dendritic cell vaccination in multiple myeloma. Int. J. Cancer 83, 215–222.

    Article  PubMed  CAS  Google Scholar 

  34. Cull, G., Durrant, L., Stainer, C., Haynes, A., and Russell, N. (1999) Generation of antiidiotype immune responses following vaccination with idiotype-protein pulsed dendritic cells in myeloma. Br. J. Haematol. 107, 648–655.

    Article  PubMed  CAS  Google Scholar 

  35. Yi, Q., Desikan, R., Barlogie, B., and Munshi, N. (2002) Optimizing dendritic cell-based immunotherapy in multiple myeloma. Br. J. Haematol. 117, 297–305.

    Article  PubMed  Google Scholar 

  36. Wen, Y. J., Min, R., Tricot, G., Barlogie, B., and Yi, Q. (2002) Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy. Blood 99, 3280–3285.

    Article  PubMed  CAS  Google Scholar 

  37. Fagerberg, J., Yi, Q., Gigliotti, D., et al. (1999) T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma. Int. J. Cancer 80, 671–680.

    Article  PubMed  CAS  Google Scholar 

  38. Hansson, L., Rabbani, H., Fagerberg, J., Osterborg, A., and Mellstedt, H. (2003) T-cell epitopes within the complementarity-determining and framework regions of the tumorderived immunoglobulin heavy chain in multiple myeloma. Blood 101, 4930–4936.

    Article  PubMed  CAS  Google Scholar 

  39. Trojan, A., Schultze, J. L., Witzens, M., et al. (2000) Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies. Nat. Med. 6, 667–672.

    Article  PubMed  CAS  Google Scholar 

  40. Gong, J., Koido, S., Chen, D., et al. (2002) Immunization against murine multiple myeloma with fusions of dendritic and plasmocytoma cells is potentiated by interleukin 12. Blood 99, 2512–2517.

    Article  PubMed  CAS  Google Scholar 

  41. Milazzo, C., Reichardt, V. L., Muller, M. R., Grunebach, F., and Brossart, P. (2003) Induction of myeloma specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA. Blood 101, 977–982.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Oncology, Immunology, and Rheumatology, University of Tübingen, Tübingen, Germany

    Volker L

Authors
  1. Volker L
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reichardt and Peter Brossart
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Research Department, Kantonsspital St. Gallen, Switzerland

    Burkhard Ludewig

  2. Department of Abdominal and Transplant Surgery, Hannover Medical School, Hannover, Germany

    Matthias W. Hoffmann

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc.

About this protocol

Cite this protocol

L, V., Brossart, R.a.P. (2005). Dendritic Cells in Clinical Trials for Multiple Myeloma. In: Ludewig, B., Hoffmann, M.W. (eds) Adoptive Immunotherapy: Methods and Protocols. Methods in Molecular Medicine™, vol 109. Humana Press. https://doi.org/10.1385/1-59259-862-5:127

Download citation

  • DOI: https://doi.org/10.1385/1-59259-862-5:127

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-406-7

  • Online ISBN: 978-1-59259-862-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation