PMID- 10587357 OWN - NLM STAT- MEDLINE DCOM- 20000113 LR - 20220330 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 190 IP - 11 DP - 1999 Dec 6 TI - 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. PG - 1669-78 AB - Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 x 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 10(6) and 12 x 10(6) DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1-specific CD8(+) cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8(+) T cell infiltration, whereas nonregressing lesions lacked CD8(+) T cells as well as Mage-3 mRNA expression. This study proves the principle that DC "vaccines" can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8(+) CTL-tumor cell interaction in situ as well as escape by lack of tumor antigen expression. FAU - Thurner, B AU - Thurner B AD - Department of Dermatology, University of Erlangen-Nuremberg, D-91052 Erlangen, Germany. FAU - Haendle, I AU - Haendle I FAU - Roder, C AU - Roder C FAU - Dieckmann, D AU - Dieckmann D FAU - Keikavoussi, P AU - Keikavoussi P FAU - Jonuleit, H AU - Jonuleit H FAU - Bender, A AU - Bender A FAU - Maczek, C AU - Maczek C FAU - Schreiner, D AU - Schreiner D FAU - von den Driesch, P AU - von den Driesch P FAU - Brocker, E B AU - Brocker EB FAU - Steinman, R M AU - Steinman RM FAU - Enk, A AU - Enk A FAU - Kampgen, E AU - Kampgen E FAU - Schuler, G AU - Schuler G LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (MAGEA3 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Tetanus Toxoid) RN - 0 (Tuberculin) SB - IM MH - Adult MH - Aged MH - Antigens, Neoplasm/immunology MH - CD8-Positive T-Lymphocytes/immunology/pathology MH - *Cancer Vaccines MH - Dendritic Cells/*immunology/*transplantation MH - Female MH - Humans MH - Immunization Schedule MH - Lung Neoplasms/*secondary/therapy MH - Lymphocytes, Tumor-Infiltrating/immunology/pathology MH - Male MH - Melanoma/*immunology/pathology/*therapy MH - Middle Aged MH - Monocytes/immunology MH - Neoplasm Metastasis MH - Neoplasm Proteins/*immunology MH - Neoplasm Staging MH - T-Lymphocytes, Cytotoxic/*immunology MH - Tetanus Toxoid/immunology MH - Tuberculin/immunology PMC - PMC2195739 EDAT- 1999/12/10 00:00 MHDA- 1999/12/10 00:01 PMCR- 2000/06/06 CRDT- 1999/12/10 00:00 PHST- 1999/12/10 00:00 [pubmed] PHST- 1999/12/10 00:01 [medline] PHST- 1999/12/10 00:00 [entrez] PHST- 2000/06/06 00:00 [pmc-release] AID - 99-0918 [pii] AID - 10.1084/jem.190.11.1669 [doi] PST - ppublish SO - J Exp Med. 1999 Dec 6;190(11):1669-78. doi: 10.1084/jem.190.11.1669.