Abstract
Dendritic cells (DC) are extremely potent antigen presenting cells, uniquely capable of sensitizing naive T cells to protein antigens and eliciting antigen specific immune responses. Studies of human DC isolated from peripheral blood indicate that these cells can be used to stimulate and expand antigen specific CD4+ and CD8+ T cells, in vitro. On the basis of these findings we have initiated pilot clinical studies to investigate the ability of DC pulsed ex vivo with tumor associated proteins to stimulate host anti-tumor immunity when re-infused as a vaccine. In the first such study DC pulsed with tumor derived idiotype protein were infused into patients with low grade malignant B cell lymphoma who had failed conventional chemotherapy. The majority of treated patients developed T cell mediated anti-idiotype immune responses and some of the patients experienced tumor regression. These results suggest that DC based immunotherapy is a potentially useful approach to B cell lymphoma and raises the possibility that the approach may prove useful in the treatment of other tumors as well.
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Bernhard H, Disis ML, Heimfeld S, Hand S, Gralow JR and Cheever MA (1995) Generation of immunostimulatory dendritic cells from human CD34+ hematopoietic progenitor cells of the bone marrow and peripheral blood. Cancer Res 55: 1099.
Carroll WL, Thielemans K, Dilley J and Levy R (1986) Mouse × human heterohybridomas as fusion partners with human B cell tumors. J Immunol Methods 89: 61.
Caux C, Dezutter DC, Schmitt C and Banchereau J (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360: 258.
Fagnoni FF, Takamizawa M, Godfrey WR, Rivas A, Azuma M, Okumura K and Engleman EG (1995) Role of B70/B7-2 in CD4+ T cell immune responses induced by dendritic cells. Immunology 85: 467–474.
Germain RN (1994) MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 76: 287–299.
Hsu FJ, Kwak L, Campbell M, Liles T, Czerwinski D, Hart S, Syrengelas A, Miller R and Levy R (1993) Clinical trials of idiotypespecific vaccine in B-cell lymphomas. Ann NY Acad Sci 690: 385–387.
Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG and Levy R (1996) Vaccination of patients with B cell lymphoma using autologous antigen pulsed dendritic cells. Nature Medicine 2: 52.
Kim D, Mitchell D, Brockstedt D, Fong L, Nolan G, Fathman CG, Engleman E and Rothbard J, Introduction of soluble proteins into both MHC class I and II pathways by conjugation to a HIV tat peptide. (submitted for publication).
Kwak LW, Campbell MJ, Czerwinski DK, Hart S, Miller RA 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.
Levy R, Hatzubia A, Brown S, Maloney D and Dilley J (1982) Immunoglobulin idiotype: A tumor-specific antigen for human B-cell lymphomas. In: Malignant Lymphomas. New York: Academic Press, Ch. 5.
Lynch RG, Rohrer JW, Odermatt B, Gebel HM, Autry JR and Hoover RG (1979) Immunoregulation of murine myeloma cell growth and differentiation: A monoclonal model of B cell differentiation. Immunol Rev 48: 45–80.
Maloney DG, Kaminski MS, Burowski D, Haimovich J and Levy R (1985) Monoclonal anti-idiotype antibodies against the murine B cell lymphoma 38C13: Characterization and use as probes for the biology of the tumor in vivo and in vitro. Hybridoma 4: 191.
Markowicz S and Engleman EG (1990) Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro. J Clin Invest 85: 955–961.
Mehta-Damani A, Markowicz S and Engleman EG (1994) Generation of antigen-specific CD8+ CTLs from naive precursors. J Immunol 153: 996–1003.
Mehta-Damani A, Markowicz S and Engleman EG (1995) Antigen specific CD4+ T cells derived from naive precursors. Eur J Immunol 25: 1206–11.
Nestle F and Nickoloff BJ (1994) Role of dendritic cells in benign and malignant lymphocytic infiltrates of the skin. Dermatol Clinics 12: 271.
Nixon DF and McMichael AJ (1991) Cytotoxic T cell recognition of HIV proteins and peptides. AIDS 5: 1045–59.
Paglia P, Chiodoni M, Rodolfo M and Colombo MP (1996) Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo. J Exp Med 183: 317.
Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM and Schuler G (1994) Proliferating dendritic cell progenitors in human blood. J Exp Med 180: 83.
Sallusto F and Lanzavecchia A (1994) 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 alpha. J Exp Med 179: 1109.
Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Ann Rev Immunol 9: 271.
Takamizawa M, Fagnoni F, Mehta-Damani A, Rivas A and Engleman EG (1995) Cellular and molecular basis of human γδ T cell activation. Role of accessory molecules in alloactivation. J Clin Invest 95: 296–303.
Takamizawa M, Rivas A, Fagnoni F, Benike C, Kosek J, Hyakawa H and Engleman EG (1997) Dendritic cells that process and present nominal antigens to naive T lymphocytes are derived from CD2+ precursors. J Immunol 158: 2134–2142.
Tsujitani S, Kakeji Y, Watanabe A, Kohnoe S, Maehara Y, Sugimachi K (1990) Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer. Cancer 66: 2012.
Zitvogel L, Mayordomo JI, Tjandrawan T, DeLeo AB, Clarke MR, Lotze MT and Storkus WJ (1996) Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. J Exp Med 183: 87.
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Engleman, E.G. Dendritic cells: Potential role in cancer therapy. Cytotechnology 25, 1–8 (1997). https://doi.org/10.1023/A:1007997918593
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DOI: https://doi.org/10.1023/A:1007997918593