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Dendritic cells: On the move from bench to bedside

Abstract

As dendritic cells increasingly become the adjuvant of choice in new approaches to cancer immunotherapy, a degree of protocol standardization is required to aid future large-scale clinical trials.

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References

  1. 1

    Banchereau, J. & Steinman, R.M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).

  2. 2

    Lotze, M.T., Shurin, M., Davis, I., Amoscato, A. & Storkus, W.J. Dendritic cell based therapy of cancer. Adv. Exp. Med. Biol. 417, 551–569 (1997).

  3. 3

    Clark, G.J. & Hart, D.N.J. Phenotypic characterization of dendritic cells. in Dendritic Cells: Biology and Clinical Applications (ed. Lotze, M.T.) 555–557 (Academic, London, 1998).

  4. 4

    Gilboa, E., Nair, S.K. & Lyerly, H.K. Immunotherapy of cancer with dendritic-cell-based vaccines. Cancer Immunol. Immunother. 46, 82–87 (1998).

  5. 5

    Young, J.W. & Inaba, K. Dendritic cells as adjuvants for class I major histocompatibility complex-restricted antitumor immunity. J. Exp.Med. 183, 7–11 (1996).

  6. 6

    Timmerman, J.M. & Levy, R. Dendritic cell vaccines for cancer immunotherapy. Annu. Rev. Med. 50, 507–529 (1999).

  7. 7

    Nestle, F.O. et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nature Med. 4, 328–332 (1998).

  8. 8

    Thurner, B. et al. Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J. Exp. Med. 190, 1669–1678 (1999).

  9. 9

    Fong, L. & Engleman, E.G. Dendritic cells in cancer immunotherapy. Annu. Rev. Immunol. 18, 245–273 (2000).

  10. 10

    Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony- stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor-α. J. Exp. Med. 179, 1109–1118 (1994).

  11. 11

    Romani, N. et al. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180, 83–93 (1994).

  12. 12

    Randolph, G.J., Inaba, K., Robbiani, D.F., Steinman, R.M. & Muller, W.A. Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity 11, 753–7561 (1999).

  13. 13

    Banchereau, J., Pulendran, B., Steinman, R. & Palucka, K. Will the making of plasmacytoid dendritic cells in vitro help unravel their mysteries? J. Exp. Med. 192 (2000).

  14. 14

    Hart, D.N.J. et al. 7th leucocyte differentiation antigen workshop dendritic cells section summary. in Leucocyte Typing Vol. VII (ed. Mason, D.) (Oxford University Press, Oxford, 2000).

  15. 15

    Schuler, G. & Steinman, R.M. Murine epidermal Langerhans cells mature into potent allostimulatory dendritic cells in vitro. J. Exp. Med. 161, 526–546 (1985).

  16. 16

    Dhodapkar, M.V. et al. Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J. Clin. Invest. 104, 173–180. (1999).

  17. 17

    Lodge, P.A., Jones, L.A., Bader, R.A., Murphy, G.P. & Salgaller, M.L. Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial. Cancer Res. 60, 829–833. (2000).

  18. 18

    Murphy, G.P. et al. Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: A phase 2 prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease. Prostate. 38, 73–78 (1999).

  19. 19

    Hsu, F.J. et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med. 2, 52–57 (1996).

  20. 20

    Dhodapkar, M.V., Steinman, R.M., Krasovsky, J., Munz, M. & Bhardwaj, N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193, 233–238 (2001).

  21. 21

    Toes, R.E. et al. Enhancement of tumor outgrowth through CTL tolerization after peptide vaccination is avoided by peptide presentation on dendritic cells. J. Immunol. 160, 4449–4456 (1998).

  22. 22

    Small, E.J. et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J. Clin. Oncol. 18, 3894–3903 (2000).

  23. 23

    Binder, R.J., Han, D.K. & Srivastava, P.K. CD91: a receptor for heat shock protein gp96. Nature Immunol. 1, 151–155 (2000).

  24. 24

    Kugler, A. et al. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nature Med. 6, 332–336 (2000).

  25. 25

    Boczkowski, D., Nair, S.K., Nam, J.H., Lyerly, H.K. & Gilboa, E. Induction of tumor immunity and cytotoxic T lymphocyte responses using dendritic cells transfected with messenger RNA amplified from tumor cells. Cancer Res. 60, 1028–1034 (2000).

  26. 26

    Vonderheide, R.H., Hahn, W.C., Schultze, J.L. & Nadler, L.M. The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 10, 673–679 (1999).

  27. 27

    Dhodapkar, M.V., Krasovsky, J., Steinman, R.M. & Bhardwaj, N. Mature dendritic cells boost functionally superior CD8(+) T-cell in humans without foreign helper epitopes. J. Clin. Invest. 105, R9–R14 (2000).

  28. 28

    Eggert, A. et al. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res. 59, 3340–3345 (1999).

  29. 29

    Barratt-Boyes, S.M. et al. Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J. Immunol. 164, 2487–2495 (2000).

  30. 30

    Thomas, R. et al. Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy. Melanoma Res. 9, 474–481 (1999).

  31. 31

    Morse, M.A. et al. Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res. 59, 56–58 (1999).

  32. 32

    Fong, L., Brockstedt, D., Benike, C., Wu, L. & Engleman, E.G. Dendritic cells injected via different routes induce immunity in cancer patients. J. Immunol. 166, 4254–4259. (2001).

  33. 33

    Serody, J.S., Collins, E.J., Tisch, R.M., Kuhns, J.J. & Frelinger, J.A. T cell activity after dendritic cell vaccination is dependent on both the type of antigen and the mode of delivery. J Immunol. 164, 4961–4967 (2000).

  34. 34

    Morse, M. et al. A phase 1 study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin. Cancer Res. 5, 1331–1338 (1999).

  35. 35

    Feuerstein, B. et al. A method for the production of cryopreserved aliquots of antigen- preloaded, mature dendritic cells ready for clinical use. J. Immunol. Meth. 245, 15–29 (2000).

  36. 36

    Ludewig, B. et al. Immunotherapy with dendritic cells directed against tumor antigens shared with normal host cells results in severe autoimmune disease. J. Exp. Med. 191, 795–803 (2000).

  37. 37

    Heiser, A. et al. Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-Cell responses against antigens expressed by primary and metastatic tumors. Cancer Res. 61, 3388–3393 (2001).

  38. 38

    Mackensen, A., Drager, R., Schlesier, M., Mertelsmann, R. & Lindemann, A. Presence of IgE antibodies to bovine serum albumin in a patient developing anaphylaxis after vaccination with human peptide-pulsed dendritic cells. Cancer Immunol. Immunother. 49, 152–156 (2000).

  39. 39

    McGuckin, M.A., MacDonald, K.P.A., Tran, M., Wykes, M. & Hart, D.N.J. MUC1 epithelial mucin—expression by normal haematopoietic cells. in Leucocyte Typing, Vol. VII (ed. Mason, D.) (Oxford University Press, Oxford, 2000).

  40. 40

    Romero, P., Cerottini, J.C. & Waanders, G.A. Novel methods to monitor antigen-specific cytotoxic T-cell responses in cancer immunotherapy. Mol. Med. Today 4, 305–312 (1998).

  41. 41

    Kammula, U.S., Marincola, F.M. & Rosenberg, S.A. Real-time quantitative polymerase chain reaction assessment of immune reactivity in melanoma patients after tumor peptide vaccination. J. Natl. Cancer Inst. 92, 1336–1344 (2000).

  42. 42

    Panelli, M.C. et al. Expansion of tumor-T cell pairs from fine needle aspirates of melanoma metastases. J. Immunol. 164, 495–504 (2000).

  43. 43

    Marincola, F.M., Jaffee, E.M., Hicklin, D.J. & Ferrone, S. Escape of human solid tumors from T-cell recognition: Molecular mechanisms and functional significance. Adv. Immunol. 74, 181–273 (2000).

  44. 44

    Hart, D.N.J. & Hill, G.R. Dendritic cell immunotherapy for cancer: application to low-grade lymphoma and multiple myeloma. Immunol. Cell Biol. 77, 451–459 (1999).

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Acknowledgements

Many of the ideas mentioned in this manuscript originate from discussions during the Expert Meeting on Dendritic Cell Clinical Trials in Zurich and the Second Annual MMRI Symposium on 'Clinical Dendritic Cell Cancer Therapy', in Brisbane, Australia.

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Correspondence to Derek Hart.

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Stephen Horwitz

Figure 2: Rationale for dendritic-cell tumor immunotherapy.

Stephen Horwitz