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)

Human melanoma antigens and their epitopes recognized by T cells have been identified using a variety of methods. These antigens are classified as 1) melanocyte specific melanosomal proteins (MART-1, gp100, tyrosinase and TRP-1), 2) proteins expressed in testis and a variety of cancers (MAGE-1, MAGE-3, BAGE and GAGE), 3) tumor specific mutated proteins (beta-catenin, MUM-1 and CDK4), and 4) others (p15). Some of the HLA-A2 binding non-mutated melanoma epitopes contained non-dominant anchor amino acids and have relatively low HLA-A2 binding affinity, suggesting that these epitopes were likely to be subdominant or cryptic self determinants. The significant correlation observed between vitiligo development and IL2 based immunotherapy suggested that autoreactive T cells specific for these self peptides were involved in melanoma regression in vivo. In addition, since adoptive transfer into patients of CTL recognizing these epitopes resulted in tumor regression, these epitopes may be tumor rejection antigens. Melanoma reactive CTL were efficiently induced from PBL of patients by in vitro stimulation with PBMC pulsed with these melanoma epitopes and may be useful in adoptive transfer protocols for the treatment of patients with metastatic melanoma. An immunization trial using the MART-1 and gp100 peptides in conjunction with incomplete Freund's adjuvant is in progress. These identified antigens may be useful for the development of new immunotherapies for the treatment of melanoma patients as well as for understanding the mechanisms of anti-tumor immune responses and autoimmune disorders against melanocytes.
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PMID:Human melanoma antigens recognized by T lymphocytes. 868 99

We have transfected human melanoma cell line 518A2 with the cDNA encoding interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF), and compared cytokine-producing clones for their ability to induce melanoma-specific cytotoxic T lymphocytes (CTL) from autologous peripheral blood mononuclear cells (PBMC) in vitro. The parental cell line expressed HLA-A1, HLA-A2, ICAM-1, LFA-3, in addition to the common CTL antigens MAGE-1, MAGE-3, tyrosinase, gp100, and Melan-A/MART-1. Stimulation of autologous PBMC responders with the IL-2-transfected clone 518/IL2.14 specifically induced CTL lines reactive with all cell lines derived from the autologous patient. Strikingly, GM-CSF-transfected 518A2 cells did not induce anti-tumor CTL reactivity. CTL induction against 518/IL2.14 was independent of HLA class II expression or CD4 help. The parental cell line 518A2 gained immunogenic properties when high concentrations of IL-2 were supplied exogenously, indicating that IL-2 produced and present at high levels locally by itself enhanced immunogenicity. From the autologous CTL line reactive with 518/IL2.14, clones were generated against an as yet unknown antigen, which was present in all autologous melanoma cell lines as well as in 7 of 15 HLA-A2+ melanoma cell lines tested, but not in melanocytes. These results will be discussed with respect to the possibility of using IL-2-transfected melanoma cells as a vaccine for treatment of patients with melanoma.
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PMID:Transfection of IL-2 augments CTL response to human melanoma cells in vitro: immunological characterization of a melanoma vaccine. 933 41

In order to construct an immunogenic cellular vaccine, we transduced three HLA-A*0201 human melanoma lines, selected for expression of classes I and II HLA, adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100 and tyrosinase, with both interleukin-2 (IL-2) and B7-1 genes by the use of a polycistronic retroviral vector. The lines were selected to share only the HLA-A*0201 allele to avoid generation of strong alloreactivity in case of their multiple in vivo use in HLA-A*0201 + patients. Phenotypic and functional analysis of B7-1-IL2 transduced melanoma lines in comparison with B7-1 transduced and/or parental untransduced counterparts were then carried out. Tumor cells expressing either B7-1 or both genes did not change their original antigenic profile. From a functional point of view, expression of both genes in melanoma lines: (1) improved the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly transduced or untransduced melanoma cells when subthreshold levels of MHC-peptide complexes were expressed by melanoma cells; (2) conferred a distinct advantage in the ability to stimulate cytotoxicity and interferon-gamma release by autologous and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA-A*0201-melanoma patients. Thus, B7-IL2 gene-transduced melanoma lines appear to display a high immunogenicity and could be used as vaccine in melanoma patients.
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PMID:Simultaneous transduction of B7-1 and IL-2 genes into human melanoma cells to be used as vaccine: enhancement of stimulatory activity for autologous and allogeneic lymphocytes. 1145 72