Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adoptive immunotherapy using CTL has provided some clinical benefit to patients with metastatic melanoma. Use of cloned CTL of known specificity might improve clinical effect, but technical difficulties have limited exploration of this possibility. We have used fluorescence-driven cell sorting to clone tumor-specific CTL after staining with tetrameric MHC class I/peptide complexes. CTL specific for the melanoma Ags melan-A, tyrosinase, and MAGE3 were cloned from the peripheral blood, tumor-infiltrated lymph nodes, and skin metastases of five patients. Clones were isolated and characterized in as little as 6 weeks, much faster than is possible with previous techniques. We show that these CTL clones express markers compatible with immunotherapeutic use in melanoma, including the cutaneous lymphocyte Ag, which is associated with homing to skin.
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PMID:Cutting edge: rapid cloning of tumor-specific CTL suitable for adoptive immunotherapy of melanoma. 1035 33

Dendritic cells (DCs) can be utilized either as vectors or as targets for therapy. Patients with metastatic melanoma received CD34-DC vaccine that contains Langerhans' cells and interstitial DCs. DCs were pulsed with MART1, tyrosinase, MAGE3, gp100 and Flu-MP peptides, and KLH. DCs induced an immune response to control antigens in 16/18 patients. An enhanced immune response to 1 or more melanoma antigens (MelAgs) was seen in these 16 patients. The two patients failing to respond experienced rapid tumour progression. Six out of seven patients with immunity to two or fewer MelAgs had progressive disease 10 weeks after study entry, in contrast to tumour progression in only 1/10 patients with immunity to > two MelAgs. Since tumour immunotherapy targets autologous antigens we can learn from systemic autoimmunity such as systemic lupus erythematosus (SLE). As opposed to normal monocytes, SLE monocytes induce proliferation of allogeneic CD4+ T cells. SLE sera induce monocyte differentiation towards DCs in an IFNalpha-dependent mechanism. Spiking autologous serum with IFNalpha reproduces DC differentiation. 50% of SLE patients have high serum levels of IFNalpha, which could explain T/B lymphopenia. Yet, plasmacytoid DCs, a major IFNalpha source, are 80% decreased. pDCs and IFNalpha may play a role in SLE pathogenesis and therapy.
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PMID:Dendritic cells: controllers of the immune system and a new promise for immunotherapy. 1460 22

Many human leukocyte antigen (HLA)-class I (mainly A*0201)-restricted peptide-specific cytotoxic T cells (CTLs) have been derived from peripheral blood lymphocytes (PBLs) of melanoma patients. However, few studies regarding HLA-A*2402-restricted melanoma-associated peptides have been performed, because HLA-A24 is not a common allele in Caucasians. In this study, we investigated the specific CTL-inducing activity of 5 HLA-A*2402-restricted peptides derived from gp100, tyrosinase, MAGE1, MAGE2 and MAGE3. A CTL induction culture was performed using PBLs and cultured dendritic cell (DC) pulsed with HLA-A*2402-restricted melanoma peptide cocktail. The CTLs derived from volunteers killed the A24 peptide-pulsed TISI cells and even HLA-A*2402-positive melanoma cells, but not HLA-A*0201-positive cells. IFN-gamma levels produced by the melanoma patients' CTLs were obviously low in each peptide group compared with those produced by the volunteers' CTLs, which indicated the presence of immunosuppressive factors in metastatic melanoma. These results suggested that polyvalent immunotherapy using multiple epitopes from melanoma antigens might be a better way of improving the efficacy of treatment.
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PMID:Cytotoxic T cell induction against human malignant melanoma cells using HLA-A24-restricted melanoma peptide cocktail. 1516 Sep 96