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5 th International September 24-28, 1998 Pittsburgh, Pennsylvania Symposium on DIANE APPLEGATE Dendritic Cells Conference Planner The in Hutton Fundamental Group 2006 East Carson Street Pittsburgh, and Clinical PA 15203 412-481-2200 Immunology 412-481-2170 FAX Organizing Committee MICHAEL T. LOTZE, M.D. University of Pgh. Cancer Inst. W1540 Biomedical Science Twr. University of Pittsburgh 200 Lothrop Street Pittsburgh, PA 15213-2582 JACQUES BANCHEREAU, Ph.D. Baylor Inst. For Immun. Research 3500 Gaston Avenue Dallas, TX 75246-2088 RALPH M. STEINMAN, M.D. Dept. Of Cell Physiology and Immun. Rockefeller University 1230 York Avenue New York, NY 10021-6399 Local Committee LOUIS FALO, OLIVERA FINN, RONALD JAFFEE, PENNY MOREL, CHARLES RI- NALDO, MICHAEL SHURIN, WALTER STORKUS, HIDEAKI TAHARA, ANGUS THOMSON, THERESA WHITESIDE, TIMO - THY WRIGHT International Committee JONATHAN AUSTYN, JACQUES BAN - CHERAU, OLIVERA FINN, ELI GILBOA, DERECK HART, PATRICK HOLT, AN - TONIO LANZAVECCHIA, CHRISTIAN LARSEN, MICHAEL LOTZE, GORDON MACPHERSON, CHARLES MALIZEW - SKI, POLLY MATZINGER, MURIEL MO - SER, ANNE O’GARRA, PAUL RACZ, PAOLA RICCIARDI- CASTAGNOLI, NI- KOLAUS ROMANI, GEROLD SCHU - LER, KEN SHORTMAN, RALPH STEIN - MAN, GEORG STINGL, WALTER STORKUS, JOHN TEW, ANGUS THOMSON August 14, 1998 R. Hoffman SIEBERTSTREET 6 MUNICH GERMANY Dear <strong>Dr</strong>. Hoffman: Your abstract titled, Isolation and priming of circulating dendritic cells with tumor antigens and heat shock proteins derived from circulating cancer cells., has been accepted for poster presentation for the 5 th international Symposium on Dendritic Cells in Fundamental and Clinical Immunology. Please check in at the conference registration desk located on the Mezzanine Level of the Hilton Hotel on Wednesday, September 23 after 4:00 PM to receive your poster number and to put up your poster. The poster number information will be included in with the first author’s registration materials. We would like you also to be present at your particular poster session to discuss your abstract with the attendees. The poster will need to be taken down by 5:00 PM on the day of your presentation. The poster boards display area is 4 foot in height and 8 foot in length. Poster can only be attached to the board by using pushpins, the pushpins will be provided for you. Your abstract will be published as submitted in the Journal of Leucocyte Biology. If you have not registered for the symposium and made your hotel accommodations please remember to do so as soon as possible and by all means prior to the first day of the symposium! If you are unable to attend the conference or if another person will be giving your presentation please let us know as soon as possible. We have had an outstanding response to this conference and look to an exciting menu at a particularly nice time in Pittsburgh. If you should have any additional questions or concerns, please call the Conference Coordinator. We certainly look forward to seeing you at the 5 th International Symposium! Sincerely yours, Michael T. Lotze, MD Professor of Surgery Molecular Genetics and Biochemistry Chief, Division of Surgical Oncology University of Pittsburgh Medical Center Phone: 412-383-9000 Fax: 412-624-1172 E-Mail: lotzemt@msx.upmc.edu 4
RESEARCH LETTERS CD83 + blood dendritic cells as a vaccine for immunotherapy of metastatic renal-cell cancer Lorenz Höltl, Claudia Rieser, Christine Papesh, Reinhold Ramoner, Georg Bartsch, Martin Thurnher Dendritic cells are the most potent stimulators of antigen-specific immune responses including antitumour responses. 1-3 Potent immunostimulatory dendritic cells can be isolated from peripheral blood or cultured from circulating precursor cells. 1-4 The safety and efficacy of these cells is now being tested in clinical trials; data from skin, prostate, and B-lymphocyte have already been published. 1-3 We did a pilot study of cultured blood dendritic cells in patients with metastatic renal-cell carcinoma 5 according to a protocol approved by the local ethical committee. Patients receive at least three intravenous infusions of activated, CD83 + dendritic cells 4 simultaneously charged with autologous tumor cell lysate and with the immunogenic protein, keyhole-limpet haemocyanin (KLH). 5-10x10 6 dendritic cells (microbiologically tested for sterility) were given per infusion. Four patients have been enrolled in the study protocol and treatment has been completed in two. One patient, a 54-year-old man, had five lung metastases with diameters of up to 3 cm and a tumour volume of more than 30 cm 3 at diagnosis as well as one skin metastasis. The skin metastasis was resected and proven to be renal-cell carcinoma with clear-cell histology. Tumour mass had increased by more than 100% in this patient between diagnosis and start of treatment (7 weeks). After two vaccinations with antigen-loaded dendritic cells, he had delayed-type hypersensitivity (DTH) reaction in response to subcutaneous injection of 5 μg of KLH. Immunohistochemical analysis of the DTH lesion revealed perivascular infiltrates predominantly consisting of T-lymphocytes. In addition, he had peripheral blood mononuclear cell (PBMC) proliferative responses against KLH and, more importantly, against cell lysates from autologous tumour and normal kidney cells (NKC). KLH-induced proliferation could partially be inhibited by monoclonal antibodies against either major histocompatibility complex class I or class II indicating the involvement of both CD4 + and CD8 + T-lymphocytes. Measurement of cytokines produced by 5 KLH-responsive cells showed interferon-γ but not interleukin-4 production indicative of a clear-cut T-helper (Th) type I immune response. Vaccination with antigen-loaded dendritic cells also induced high titres of anti-KLH antibodies (IgM and IgG) and antibodies (IgM but not IgG) against renal-cell carcinoma and NKC lysates although at a much lower level. He became feverish (38•5-40 o C) within a few hours of the second and third injection in the absence of detectable viral or bacterial infection. The onset of fever after the second infusion coincided with a halt in tumour growth. The arrest of tumour growth was accompanied by the disappearance of haemoptysis. 4 weeks after the third vaccination, regression of all lung metastases was observed (59%, 72%, 52%, 98%, 35%) with an overall regression of tumour mass of 61%. Further regression of the metastases was noted after the fourth vaccination. A biopsy specimen taken from a regressing metastasis showed only a few vital epithelial cells surrounded by numerous T-lymphocytes. Our observation confirm the capability of cultured dendritic cells to stimulate a strong antigen-specific Th1 type immune response in a patient with metastatic renal-cell cancer even in the presence of a large tumour burden. We thank A. Stenzl for critical reading of the manuscript, our other colleagues from Deparment of Urology and H. Rogatsch from the Institute of Pathology, and the Austrian Science Fund for financial support (project no P11758MED to MT) 1) Banchereau J, Steinmann RM, Dendritic cells and the control of immunity. Nature 1998; 392: 245-52. 2) Nestle FO, Alijagic S, Gilliet M, et al. Vaccination of melanoma patients with peptide - or tumor lysate-pulsed dendritic cells. NatMed 1998; 4: 328-32 3) Murphy G, Tjoa B, Ragde H, Kenny G, Boynton A. Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate 1996; 29: 371-80 4) Rieser C, Böck G, Klocker H, Bartsch G, Thurnher M. Prostaglandin E2 and tumor necrosis factor alpha cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production. J Exp Med 1997; 186: 1603-08. 5) Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med 1996; 335: 865-75 Department of Urology, University of Innsbruck, 6020 Innsbruck, Austria (M Thurnher) THE LANCET • Vol 352 • October 24, 1998
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