Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characterization of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer therapy. Several categories of cancer-associated antigens have been described as targets for cytotoxic T lymphocytes (CTLs) in vitro and in vivo: "cancer-testis" (CT) antigens expressed in different tumors and normal testis, melanocyte differentiation antigens, point mutations of normal genes, antigens that are overexpressed in malignant tissues, and viral antigens. Clinical studies using peptides derived from these antigens have been initiated to induce specific CTL responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined, i.e., induction of delayed-type hypersensitivity (DTH), CTL, autoimmune, and tumor regression responses. Preliminary results demonstrate that tumor-associated peptides alone elicit specific DTH and CTL responses leading to tumor regression after intradermal injection. GM-CSF was proved to be effective in enhancing peptide-specific immune reactions by amplification of dermal peptide-presenting dendritic cells. Long-lasting complete tumor regressions have been observed after induction of CTLs by peptide immunization. However, in a few cases where there was disease progression after initial tumor response, loss of either the tumor antigen targeted by CTLs or of the presenting MHC class I molecule was detected as the mechanism of immune escape under immunization in vivo. Based on these observations, cytokines to enhance antigen and MHC class I expression in vivo are being evaluated to prevent immunoselection. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1. In a melanoma patient with high titer antibody against NY-ESO-1, strong HLA-A2-restricted CTL reactivity against the same antigen was also found. Clinical studies involving tumor antigens that induce both antibody and CTL responses will show whether these are better candidates for immunotherapy of cancer.
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PMID:Strategies for the development of vaccines to treat breast cancer. 992 50

The characterization of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer therapy. Several categories of cancer-associated antigens have been described as targets for cytotoxic T lymphocytes (CTL) in vitro and in vivo: (1) 'Cancer-Testis' (CT) antigens expressed in different tumors and normal testis, (2) melanocyte differentiation antigens, (3) point mutations of normal genes, (4) antigens that are overexpressed in malignant tissues, and (5) viral antigens. Clinical studies with peptides derived from these antigens have been initiated to induce specific CTL responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined, i.e. induction of DTH-, CTL-, autoimmune-, and tumor-regression responses. Preliminary results demonstrate that tumor-associated peptides alone elicit specific DTH- and CTL-responses leading to tumor regression after intradermal injection. GM-CSF was proven effective to enhance peptide-specific immune reactions by amplification of dermal peptide-presenting dendritic cells. Long lasting complete tumor regressions have been observed after induction of CTL by peptide immunization. Based on these results, active immunotherapy with tumor-associated antigens may be a promising approach for patients with minimal residual disease, who are at high risk for tumor recurrence. However, in single cases with disease progression after an initial tumor response either a loss of the respective tumor antigen targeted by CTL or of the presenting MHC class I molecule was detected as mechanisms of immune escape under immunization in vivo. Based on these observations, cytokines to enhance antigen- and MHC-class I expression in vivo are being evaluated to prevent immunoselection. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1. In a melanoma patient with high titer antibody against NY-ESO-1 also a strong HLA-A2 restricted CTL reactivity against the same antigen was found. Clinical studies involving tumor antigens that induce both antibody- and CTL-responses will show whether these are better candidates for immunotherapy of cancer.
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PMID:CTL-defined cancer vaccines: perspectives for active immunotherapeutic interventions in minimal residual disease. 1050 52

The identification of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer therapy. Different groups of cancer-associated antigens have been described as targets for cytotoxic T lymphocytes (CTLs) in vitro and in vivo: 1) cancer-testis (CT) antigens, which are expressed in different tumors and normal testis; 2) melanocyte differentiation antigens; 3) point mutations of normal genes; 4) antigens that are overexpressed in malignant tissues; and 5) viral antigens. Clinical studies with peptides derived from these antigens have been initiated to induce specific CTL responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined, i.e., delayed-type hypersensitivity (DTH), CTL, autoimmmune, and tumor regression responses. Preliminary results demonstrate that tumor-associated peptides alone elicit specific DTH and CTL responses leading to tumor regression after intradermal injection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was proven effective in enhancing peptide-specific immune reactions by amplification of dermal peptide-presenting dendritic cells. Long-lasting complete tumor regressions have been observed after induction of peptide-specific CTLs. However, in single cases with disease progression after an initial tumor response, either a loss of the respective tumor antigen targeted by CTLs or of the presenting major histocompatibility complex (MHC) class I allele was detected as a mechanism of immune escape under immunization. Based on these observations, cytokines to enhance antigen and MHC class I expression in vivo are being evaluated to prevent immunoselection. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1, which is regarded as one of the most immunogenic antigens known today inducing spontaneous immune responses in 50% of patients with NY-ESO-1-expressing cancers. Clinical studies involving antigenic constructs that induce both antibody and CTL responses will show whether these are more effective for immunotherapy of cancer.
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PMID:Cancer immunotherapy in clinical oncology. 1095 Jan 48

The identification of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer immunotherapy. Different categories of cancer-associated antigens have been described as targets for CD8+ T cells in vitro and in vivo: (1) 'cancer-testis' (CT) antigens expressed in different tumors and normal testis; (2) melanocyte differentiation antigens; (3) point mutations of normal genes; (4) antigens that are overexpressed in malignant tissues, and (5) viral antigens. Clinical trials with antigenic peptides have been initiated to induce specific immunological responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined: DTH, CD8+ T cell, autoimmune and tumor regression responses. Preliminary results show that tumor-associated peptides alone elicit specific DTH and CD8+ T cell responses associated with tumor regression after intradermal vaccination. Granulocyte macrophage colony-stimulating factor has been shown to enhance peptide-specific immune reactions by amplification of dermal antigen-presenting dendritic cells. Complete tumor regressions have been observed after the induction of CD8+ T cell responses by peptide immunization. Based on these results, active immunotherapy with tumor-associated antigens may be a promising approach for patients in adjuvant treatment situations, who are at high risk for tumor recurrence. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1. NY-ESO-1-specific spontaneous humoral and cellular immune responses were found in approximately 50% of patients with NY-ESO-1-positive tumors. Clinical studies have been initiated to evaluate the immunological effects of immunization with NY-ESO-1 peptides in cancer patients with detectable or absent immunity against NY-ESO-1.
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PMID:Vaccination for malignant melanoma: recent developments. 1115 Sep 1

Tumor-associated antigens recognized by cellular or humoral effectors of the immune system represent attractive targets for antigen-specific cancer therapy. Different groups of cancer-associated antigens have been identified inducing cytotoxic T-lymphocyte (CTL) responses in vitro and in vivo: 1) 'Cancer-Testis' (CT) antigens, which are expressed in different tumors and normal testis, 2) melanocyte differentiation antigens, 3) point mutations of normal genes, 4) antigens that are overexpressed in malignant tissues, and 5) viral antigens. Clinical studies with peptides derived from these antigens have been initiated to study the induction of specific CTL responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined, i. e., delayed-type hypersensitivity (DTH), CTL, autoimmune, and tumor regression responses. Early results show that tumor-associated peptides alone induce specific DTH and CTL responses and tumor regression after intradermal administration. GM-CSF was used as an adjuvant to enhance peptide-specific immune reactions by amplification of dermal peptide-presenting dendritic cells. Complete tumor regressions have been observed in the context of measurable peptide-specific CTL. However, in single cases with disease progression after an initial tumor response, either a loss of the respective tumor antigen targeted by CTL or of the presenting MHC class I allele was detected, suggesting immunization-induced immune escape. Based on these observations, cytokines to modify antigen and MHC class I expression in vivo are being tested to prevent immunoselection. Recently, a new CT antigen, NY-ESO-1, has been identified with a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX). NY-ESO-1 is regarded as one of the most immunogenic antigens known today, inducing spontaneous immune responses in 50% of patients with NY-ESO-1-expressing cancers. Clinical studies with antigenic constructs to induce both humoral and cellular immune responses will show whether these are more effective for immunotherapy of cancer. Copyright 2000 S. Karger GmbH, Freiburg
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PMID:Peptide Vaccination in Clinical Oncology. 1144 Dec 34

The infiltration of tumors by T cells has been shown to correlate with prolonged patients' survival. However, it remains unclear why only some tumors are infiltrated with T cells. This study was designed to investigate possible correlations between intratumoral T-cell infiltrates and the expression of cancer-associated antigens and MHC class I and II molecules in patients with melanoma. Fresh frozen samples from 124 stage IV melanoma patients were analyzed by immunohistochemistry for the expression of Melan-A/MART-1, tyrosinase, gp100, NY-ESO-1, and MHC class I and II. Intratumoral T-cell and B-cell infiltrates were detected by staining with anti-CD4, anti-CD8, anti-CD3, and L26 antibodies. The NY-ESO-1 serum antibody status was assessed by Western blot analysis. Intratumoral CD8+ and CD4+ T cells were detected in 63.9% and 71.3% of patients, respectively. We observed a significant heterogeneity of the expression of the melanocyte differentiation antigens, NY-ESO-1, and MHC class I and II molecules. The only significant correlation was found between the expression of MHC class I and the presence of CD4+ and CD8+ T cells (P < 0.0001). There was a strong association between these two variables with respect to the density and distribution of infiltrating T cells and the pattern of MHC class I expression (focal versus homogenous). Intratumoral T-cell infiltration is closely correlated with the MHC class I expression but not with the expression of differentiation antigens, cancer-associated antigens, or MHC class II molecules. These results may have implications for the definition of prognostic variables and for the identification of patients who may benefit from antigen-specific cancer immunotherapy.
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PMID:Intratumoral T-cell infiltrates and MHC class I expression in patients with stage IV melanoma. 1586 94

The cancer-associated antigen NY-ESO-1 is expressed in a number of malignancies of different histological type. Patients with NY-ESO-1 expressing tumors have been shown to bear circulating autoantibodies against this antigen. In this study, we have assessed the NY-ESO-I autoantibody response in patients with lung cancer by a serum ELISA. Using a serum dilution of 1:400 we detected seroreactivity in 35 of 175 (20%) of patients. Incidence of autoantibodies was significantly higher in patients suffering from non small cell lung cancer (NSCLC, 23%) as compared to those with small cell lung cancer (SCLC, 9%). In the NSCLC group, NY-ESO-I antibody was significantly more frequent in patients with undifferentiated tumors (40%) as compared to patients with either adenocarcinoma or squamous cell carcinoma (15 and 29%). Our observations indicate that induction of NY-ESO-I autoantibodies depends on the histological subtype within a given tumor entity.
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PMID:Humoral immune responses of lung cancer patients against tumor antigen NY-ESO-1. 1599 94

Cancer testis (CT) antigens are promising candidates for tumor vaccines due to their immunogenicity and tissue-restricted expression. Recently, we identified a novel cancer testis gene, BORIS, whose expression is restricted to male testis after puberty and is strictly absent in non-malignant female tissue. BORIS encodes a DNA-binding protein that shares 11 zing finger (ZF) with transcription factor CTCF and differs at the N- and C-termini. CTCF has been implicated in epigenetic regulation of imprinting, X chromosome inactivation, repression, and activation of cancer testis antigens. BORIS expression has been documented in cancers of diverse histological origin, including, but not limited to breast, prostate, ovary, gastric, liver, endometrial, glia, colon, and esophagus. Interestingly, BORIS induces demethylation and subsequent expression of many cancer-testis genes, including MAGE-A1 and NY-ESO-1, indicating that it is expressed very early in malignancy and might be an attractive candidate for immunotherapy. In this study we tested BORIS as a vaccine in a very aggressive, highly metastatic, and poorly immunogenic murine model of mammary carcinoma. Immunizations with a DNA encoding the mutant form of murine BORIS antigen (pmBORIS lacking DNA-binding function) significantly prolonged survival, and inhibited tumor growth in BALB/c mice inoculated with 4T1 cells. Priming with pmBORIS mixed with molecular adjuvant and boosting with adenoviral vector expressing mBORIS was generally more effective, suggesting that the vaccination protocol could be further optimized. This is the first report demonstrating the feasibility of vaccination with a cancer associated epigenetic regulator for the induction of tumor inhibition.
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PMID:Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. 1674 71

Cancer-Testis (CT) antigens are by definition expressed in tumor but not in healthy tissue except testis and might represent ideal targets for antigen-specific immunotherapy. Here, we present the first comprehensive analysis of CT antigen expression in patients with head and neck squamous cell carcinoma (HNSCC). Tumor samples (N = 51), and adjacent healthy tissue from patients with HNSCC were analyzed for the expression of 23 genes designated CT antigens using RT-PCR. Patient sera (N = 39) were screened for IgG antibody responses against NY-ESO-1, MAGEA3, and SSX2. According to their expression pattern antigens were divided into four groups. ADAM2, LIP1, SLLP1, AKAP3, CTAGE, ZNF165, CAGE, and FTHL17 were expressed in tumor and healthy tissue at comparable frequencies. NY-TLU-57, GAGE1, SAGE1 were expressed more frequently in tumor samples than in healthy tissues. TPTE, LDHC, SPO11 were expressed neither in tumor samples nor in healthy tissue. 9 CT antigens were expressed only in the tumor tissue and may represent ideal candidates for active immunotherapy in HNSCC: MAGEA3 was expressed in 72%, SSX1 in 45%, MAGEC2 in 33%, MAGEC1 in 28%, BAGE in 17%, SSX2 in 16%, SCP1 in 12%, NY-ESO-1 in 6%, and HOM-TES-85 in 4% of cases. 86% of tumor samples expressed at least one, 69% expressed at least two, and 43% expressed at least three of these antigens. Three patients showed an antibody response against NY-ESO-1. In conclusion, we demonstrate here that HNSCC frequently express CT antigens. Furthermore, a relatively high percentage of tumors express more than one CT antigen opening the perspective for polyvalent antigen-specific immunotherapy.
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PMID:Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma. 1702 87

CHP-NY-ESO-1 is a novel therapeutic cancer vaccine consisting of a recombinant protein of cancer antigen NY-ESO-1 and a polysaccharide-based delivery system, cholesteryl pullulan. A pilot clinical study of CHP-NY-ESO-1 in cancer patients was previously conducted, and the adverse events related to this drug were observed to be limited to skin reactions at injection sites. To further establish the safety of CHP-NY-ESO-1, we studied the effects of its subcutaneous injection on vital functions such as the central nervous system, cardiovascular system and respiratory system using preclinical animal models. The effects of CHP-NY-ESO-1 on the cardiovascular system were investigated in dogs using a telemetry system for blood pressure and heart rate and the Holter monitoring for ambulatory electrocardiograms. No drug-related changes were observed in these parameters. The effect of CHP-NY-ESO-1 on the hERG-dependent potassium currents was also examined using in vitro cultured cell system, and no inhibition of hERG currents was observed. The effects of CHP-NY-ESO-1 on the central nervous system were examined in rats using functional observational battery method, and no drug-related changes were observed in home cage observations, open field observations, hand held observations, and perception and motor function observations. The effect of CHP-NY-ESO-1 on the respiratory system was investigated in rats by measuring tidal volume, minute volume and respiratory rate using whole-body plethysmograph method, and no significant changes were found in these parameters. These results indicate that CHP-NY-ESO-1 would not have any pharmacological effects on vital functions and support the safety of this cancer vaccine for clinical use.
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PMID:Preclinical safety pharmacology study of a novel protein-based cancer vaccine CHP-NY-ESO-1. 1877 6


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