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 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 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.

Dendritic cell (DC) vaccination, albeit still in an early stage, is a promising strategy to induce immunity to cancer. We explored whether DC can expand Ag-specific CD8+ T cells even in far-advanced stage IV melanoma patients. We found that three to five biweekly vaccinations of mature, monocyte-derived DC (three vaccinations of 6 × 106 s.c. followed by two i.v. ones of 6 and 12 × 106, respectively) pulsed with Mage-3A2.1 tumor and influenza matrix A2.1-positive control peptides as well as the recall Ag tetanus toxoid (in three of eight patients) generated in all eight patients Ag-specific effector CD8+ T cells that were detectable in blood directly ex vivo. This is the first time that active, melanoma peptide-specific, IFN-γ-producing, effector CD8+ T cells have been reliably observed in patients vaccinated with melanoma Ags. Therefore, our DC vaccination strategy performs an adjuvant role and encourages further optimization of this new immunization approach.

No abstract

No abstract

Granuloma annulare (GA) is a chronic inflammatory disorder of unknown aetiology, which is characterized clinically by erythematous plaques preferentially localized to the distal extremities, although disseminated variants exist. In light of the chronic relapsing nature of GA and lack of satisfactory treatment options, we initiated treatment with infliximab in a patient with chronic disseminated GA that was recalcitrant to standard treatment. The 59-year-old female patient with insulin-dependent diabetes had experienced GA lesions for more than 4 years despite various systemic and topical treatments. Systemic glucocorticoids were not a therapeutic option because of the preexisting unstable insulin-dependent diabetes. Infliximab was administered intravenously at 5 mg kg(-1) day(-1) at weeks 0, 2 and 6 and thereafter at a monthly interval for an additional 4 months. Most of the GA plaques resolved within 4-6 weeks, leaving postinflammatory brownish macules. Newly arising plaques disappeared within 2 weeks and new GA lesions were not observed during the entire observation period of more than 16 months. Infliximab may be an additional option in the treatment of recalcitrant forms of GA as well as in other chronic granulomatous skin disorders, such as sarcoidosis and necrobiosis lipoidica.