PMID- 16971810 OWN - NLM STAT- MEDLINE DCOM- 20061114 LR - 20201226 IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 29 IP - 5 DP - 2006 Sep-Oct TI - Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity. PG - 545-57 AB - Dendritic cells (DCs) loaded with killed allogeneic tumors can cross-prime tumor-specific naive CD8 T cells in vitro, thereby providing an option to overcome human leukocyte antigen restriction inherent to loading DC vaccines with peptides. We have vaccinated 20 patients with stage IV melanoma with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line. DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand. A total of 8 vaccines were administered at monthly intervals. The first patient was accrued December 2002 and the last November 2003. Fourteen patients were alive at 12 months, 9 patients were alive at 24 months, and 8 patients are alive as of January 2006. The estimated median overall survival is 22.5 months with a range of 2 to 35.5 months. Vaccinations were safe and tolerable. They induced, in 2 patients who failed previous therapy, durable objective clinical responses, 1 complete regression (CR) and 1 partial regression (PR) lasting 18 and 23 months, respectively. Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen. Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides. In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred. Thus, the present results justify the design of larger follow-up studies to assess the clinical response to DC vaccines loaded with killed allogeneic tumor cells in patients with metastatic melanoma. FAU - Palucka, Anna K AU - Palucka AK AD - Baylor Institute for Immunology Research, Sammons Cancer Center, 3434 Live Oak, Dallas, TX 75204, USA. karolinp@baylorhealth.edu FAU - Ueno, Hideki AU - Ueno H FAU - Connolly, John AU - Connolly J FAU - Kerneis-Norvell, Fabienne AU - Kerneis-Norvell F FAU - Blanck, Jean-Philippe AU - Blanck JP FAU - Johnston, Dennis A AU - Johnston DA FAU - Fay, Joseph AU - Fay J FAU - Banchereau, Jacques AU - Banchereau J LA - eng GR - CA 085540/CA/NCI NIH HHS/United States GR - CA 89440/CA/NCI NIH HHS/United States GR - P01 CA 84512/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (HLA-A2 Antigen) RN - 0 (MART-1 Antigen) RN - 0 (MLANA protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Peptides) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Aged MH - Antigens, Neoplasm/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Cancer Vaccines/adverse effects/*therapeutic use MH - Cell Differentiation MH - Cell Line, Tumor MH - Cross-Priming MH - Cytotoxicity, Immunologic MH - Dendritic Cells/cytology/*immunology MH - HLA-A2 Antigen/immunology MH - Humans MH - Immunotherapy, Adoptive MH - Interferon-gamma/metabolism MH - MART-1 Antigen MH - Melanoma/immunology/pathology/*therapy MH - Middle Aged MH - Monocytes/cytology/immunology MH - Neoplasm Metastasis MH - Neoplasm Proteins/*immunology MH - Peptides/immunology MH - Skin Neoplasms/immunology/pathology/*therapy MH - Survival Rate MH - Transplantation, Homologous EDAT- 2006/09/15 09:00 MHDA- 2006/11/15 09:00 CRDT- 2006/09/15 09:00 PHST- 2006/09/15 09:00 [pubmed] PHST- 2006/11/15 09:00 [medline] PHST- 2006/09/15 09:00 [entrez] AID - 00002371-200609000-00009 [pii] AID - 10.1097/01.cji.0000211309.90621.8b [doi] PST - ppublish SO - J Immunother. 2006 Sep-Oct;29(5):545-57. doi: 10.1097/01.cji.0000211309.90621.8b.