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Soldano Ferrone - One of the best experts on this subject based on the ideXlab platform.

  • a high molecular weight melanoma associated Antigen specific chimeric Antigen receptor redirects lymphocytes to target human melanomas
    Cancer Research, 2010
    Co-Authors: William R Burns, Steven A Rosenberg, Soldano Ferrone, Yangbing Zhao, Timothy L Frankel, Christian S Hinrichs, Zhili Zheng, Hui Xu, Steven A Feldman, Richard A Morgan
    Abstract:

    Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte Antigen (HLA) class I Antigen–restricted, melanoma Antigen–reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non–MHC-restricted, chimeric Antigen receptor (CAR) targeting the high molecular weight Melanoma-Associated Antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA–specific CARs containing an Antigen recognition domain based on variations of the HMW-MAA–specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3ζ activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA–specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA–expressing cell lines. Furthermore, the receptor functioned in both CD4+ and CD8+ cells, was non–MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA–specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. Cancer Res; 70(8); 3027–33. ©2010 AACR.

  • mrna expression and braf mutation in circulating melanoma cells isolated from peripheral blood with high molecular weight melanoma associated Antigen specific monoclonal antibody beads
    Clinical Chemistry, 2009
    Co-Authors: Minoru Kitago, Donald L. Morton, Soldano Ferrone, Kazuo Koyanagi, Takeshi Nakamura, Yasufumi Goto, Mark B Faries, Steven J Oday, Dave S. B. Hoon
    Abstract:

    Background: The detection of circulating tumor cells (CTCs) in the peripheral blood of melanoma patients by quantitative real-time reverse-transcription PCR (qRT-PCR) analysis correlates with a poor prognosis. The assessment of CTCs from blood has been difficult because of lack of a good monoclonal antibody (mAb) directed against surface cell Antigens to capture melanoma cells. Methods: Blood was collected prospectively from 57 melanoma patients (43 test and 14 test-development cases) and 5 healthy donors. High molecular weight Melanoma-Associated Antigen (HMW-MAA)-specific mAbs bound to immunomagnetic beads were used to isolate CTCs. mRNA and/or DNA were extracted from CTCs. Testing for the expression of a Melanoma-Associated gene panel ( MLANA , MAGEA3 , and MITF ) with qRT-PCR and for the presence of BRAF mt (a BRAF gene variant encoding the V600E mutant protein) verified the beads-isolated CTCs to be melanoma cells. A peptide nucleic acid-clamping PCR assay was used for BRAF mt analysis. Results: Spiking of peripheral blood cells (PBCs) with melanoma cells showed that the beads-based detection assay can detect approximately 1 melanoma cell in 5 × 106 PBCs. qRT-PCR analysis detected MLANA , MAGEA3 , and MITF expression in 19 (44%), 29 (67%), and 19 (44%) of the patients, respectively. At least one biomarker of the panel was positive in 40 (93%) of the 43 melanoma patients. BRAF mt was detected in 17 (81%) of the 21 assessed stage IV melanoma patients. Conclusion: The assay of bead capture coupled with the PCR has utility for assessing CTCs in melanoma patients, which can then be characterized for both genomic and transcriptome expression.

  • cancer immunotherapy targeting the high molecular weight melanoma associated Antigen protein results in a broad antitumor response and reduction of pericytes in the tumor vasculature
    Cancer Research, 2008
    Co-Authors: Paulo Maciag, Soldano Ferrone, Matthew M Seavey, Yvonne Paterson
    Abstract:

    The high molecular weight Melanoma-Associated Antigen (HMW-MAA), also known as melanoma chondroitin sulfate proteoglycan, has been used as a target for the immunotherapy of melanoma. This Antigen is expressed on the cell surface and has a restricted distribution in normal tissues. Besides its expression in a broad range of transformed cells, this Antigen is also found in pericytes, which are important for tumor angiogenesis. We generated a recombinant Listeria monocytogenes ( Lm -LLO-HMW-MAA-C) that expresses and secretes a fragment of HMW-MAA (residues 2,160–2,258) fused to the first 441 residues of the listeriolysin O (LLO) protein. Immunization with Lm -LLO-HMW-MAA-C was able to impede the tumor growth of early established B16F10-HMW-MAA tumors in mice and both CD4+ and CD8+ T cells were required for therapeutic efficacy. Immune responses to a known HLA-A2 epitope present in the HMW-MAA2160-2258 fragment was detected in the HLA-A2/Kb transgenic mice immunized with Lm -LLO-HMW-MAA-C. Surprisingly, this vaccine also significantly impaired the in vivo growth of other tumorigenic cell lines, such as melanoma, renal carcinoma, and breast tumors, which were not engineered to express HMW-MAA. One hypothesis is that the vaccine could be targeting pericytes, which are important for tumor angiogenesis. In a breast tumor model, immunization with Lm -LLO-HMW-MAA-C caused CD8+ T-cell infiltration in the tumor stroma and a significant decrease in the number of pericytes in the tumor blood vessels. In conclusion, a Lm -based vaccine against HMW-MAA can trigger cell-mediated immune responses to this Antigen that can target not only tumor cells but also pericytes in the tumor vasculature. [Cancer Res 2008;68(19):8066–75]

  • targeting melanoma cells with human high molecular weight melanoma associated Antigen specific antibodies elicited by a peptide mimotope functional effects
    Journal of Immunology, 2006
    Co-Authors: Eric C Ko, Xinhui Wang, Soldano Ferrone
    Abstract:

    Human high molecular weight-melanoma associated Ag (HMW-MAA) mimics have been shown to elicit HMW-MAA-specific humoral immune responses that appear to be clinically beneficial. This finding has stimulated interest in characterizing the mechanism(s) underlying the ability of the elicited Abs to exert an anti-tumor effect. To address this question, in the present study, we have generated HMW-MAA-specific Abs by sequentially immunizing rabbits with the peptide P763.74, which mimics the HMW-MAA determinant recognized by mAb 763.74, and with HMW-MAA + melanoma cells. HMW-MAA-specific Abs isolated from immunized rabbits mediated cell-dependent cytotoxicity but did not mediate complement-dependent cytotoxicity of HMW-MAA + melanoma cells. These Abs also effectively inhibited spreading, migration and Matrigel invasion of HMW-MAA + melanoma cells. Besides contributing to our understanding of the role of HMW-MAA in the biology of melanoma cells, these results suggest that both immunological and nonimmunological mechanisms underlie the beneficial clinical effects associated with the induction of HMW-MAA-specific Abs in melanoma patients immunized with a HMW-MAA mimic.

  • functional idiotopes tumor Antigen directed expression of cd8 t cell epitopes nested in unique nh2 terminal vh sequence of antiidiotypic antibodies
    Cancer Research, 2005
    Co-Authors: Kouichiro Kawano, Soldano Ferrone, Constantin G Ioannides
    Abstract:

    Antiidiotypic antibodies have been and are being used for cancer immunotherapy based on the rationale that Ab2 carrying an “internal image” of the corresponding tumor Antigen can induce tumor Antigen–specific antibodies (i.e., Ab3 and inhibit tumor growth). Recent evidence indicates that Ab2 also induces cellular responses by CD4+ and CD8+ T cells. This finding has raised the question of where the short peptides, which express CD8+ T-cell–defined epitopes, are located and their relationship with the tumor Antigen. We found that two of the four known Ab2 associated with tumor Antigen, with known amino acid sequence, express unique NH2-terminal VH sequences which precede the framework regions. Both the unique and the shared NH2-terminal VH sequences are nested MHC class I Antigen–binding peptides. These peptides were highly homologous with peptides from corresponding tumor Antigen (carcinoembryonic Antigen, CD55, and human high molecular weight melanoma–associated Antigen) but differed from the tumor Antigen peptides by the presence of the side chain known to mediate stronger forces of interaction with other atoms. The presence of candidate CTL epitopes in NH2-terminal VH of Ab2 homologous with tumor Antigen may be important for the development of novel immunotherapeutic strategies for cancer.

Abeer A Bahnassy - One of the best experts on this subject based on the ideXlab platform.

  • abstract 3540 evaluation of alpha fetoprotein afp telomerase melanoma associated Antigen mage1 and mage 3 cancer stem cell markers cytokeratin ck and cd133 as potential biomarkers for hepatocellular carcinoma hcc
    Cancer Research, 2013
    Co-Authors: Abdelrahman N Zekri, Abeer A Bahnassy
    Abstract:

    Background. Hepatocellular carcinoma (HCC) had been recently classified as a complex disease with a wide range of risk factors. Analysis of AFP level as a tumor marker is applied in patients with a high risk of developing HCC. However, the lack of AFP sensitivity and specificity has elucidated the need for novel tumor markers. Therefore, the aim of the current study is to assess AFP, MAGE1 and MAGE 3, CK, and HCC cancer stem cell (CSC) markers (CD133, CD90, CD44) as potential biomarkers for HCC patients. Patients and Methods. This study was conducted on the peripheral blood lymphocytes (PBL) of one 130 participants involving 70 patients with HCC, thirteen patients with chronic hepatitis (CH) and 30 normal controls. For those patients, serum AFP was tested by ELISA. Telomerase, MAGE 1, and MAGE 3, CD90 and CD44 RNA expression was detected by qualitative reverse transcriptase-polymerase chain reaction (qPCR). CD133 and CK expression was measured by flowcytometry (FCM) and qPCR analysis in 10 ml of PBL of each patient. Results. All CH and HCC patients were positive for HCV antibodies. The number of cells expressing CD 133 in the patients PBL was significantly lower in HCC patients than other groups while that of CD90 and CD44 was significantly higher in HCC than in the other groups (p Conclusion. 1) AFP, MAGE1, MAGE 3 and the number of cells expressing CK in the PBL of HCC could be used as markers for early detection of HCC. 2) The CSC markers (CD90, CD44) and AFP are highly expressed in HCC and contribute to aggressive phenotype thus they could be used as prognostic and predictive markers. Citation Format: Abdel-Rahman N. Zekri, Abeer Bahnassy. Evaluation of Alpha-fetoprotein (AFP), telomerase, melanoma associated Antigen (MAGE1 and MAGE 3), cancer stem cell markers cytokeratin (CK) and (CD133,) as potential biomarkers for hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3540. doi:10.1158/1538-7445.AM2013-3540

  • abstract 3540 evaluation of alpha fetoprotein afp telomerase melanoma associated Antigen mage1 and mage 3 cancer stem cell markers cytokeratin ck and cd133 as potential biomarkers for hepatocellular carcinoma hcc
    Cancer Research, 2013
    Co-Authors: Abdelrahman N Zekri, Abeer A Bahnassy
    Abstract:

    Background. Hepatocellular carcinoma (HCC) had been recently classified as a complex disease with a wide range of risk factors. Analysis of AFP level as a tumor marker is applied in patients with a high risk of developing HCC. However, the lack of AFP sensitivity and specificity has elucidated the need for novel tumor markers. Therefore, the aim of the current study is to assess AFP, MAGE1 and MAGE 3, CK, and HCC cancer stem cell (CSC) markers (CD133, CD90, CD44) as potential biomarkers for HCC patients. Patients and Methods. This study was conducted on the peripheral blood lymphocytes (PBL) of one 130 participants involving 70 patients with HCC, thirteen patients with chronic hepatitis (CH) and 30 normal controls. For those patients, serum AFP was tested by ELISA. Telomerase, MAGE 1, and MAGE 3, CD90 and CD44 RNA expression was detected by qualitative reverse transcriptase-polymerase chain reaction (qPCR). CD133 and CK expression was measured by flowcytometry (FCM) and qPCR analysis in 10 ml of PBL of each patient. Results. All CH and HCC patients were positive for HCV antibodies. The number of cells expressing CD 133 in the patients PBL was significantly lower in HCC patients than other groups while that of CD90 and CD44 was significantly higher in HCC than in the other groups (p Conclusion. 1) AFP, MAGE1, MAGE 3 and the number of cells expressing CK in the PBL of HCC could be used as markers for early detection of HCC. 2) The CSC markers (CD90, CD44) and AFP are highly expressed in HCC and contribute to aggressive phenotype thus they could be used as prognostic and predictive markers. Citation Format: Abdel-Rahman N. Zekri, Abeer Bahnassy. Evaluation of Alpha-fetoprotein (AFP), telomerase, melanoma associated Antigen (MAGE1 and MAGE 3), cancer stem cell markers cytokeratin (CK) and (CD133,) as potential biomarkers for hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3540. doi:10.1158/1538-7445.AM2013-3540

Abdelrahman N Zekri - One of the best experts on this subject based on the ideXlab platform.

  • abstract 3540 evaluation of alpha fetoprotein afp telomerase melanoma associated Antigen mage1 and mage 3 cancer stem cell markers cytokeratin ck and cd133 as potential biomarkers for hepatocellular carcinoma hcc
    Cancer Research, 2013
    Co-Authors: Abdelrahman N Zekri, Abeer A Bahnassy
    Abstract:

    Background. Hepatocellular carcinoma (HCC) had been recently classified as a complex disease with a wide range of risk factors. Analysis of AFP level as a tumor marker is applied in patients with a high risk of developing HCC. However, the lack of AFP sensitivity and specificity has elucidated the need for novel tumor markers. Therefore, the aim of the current study is to assess AFP, MAGE1 and MAGE 3, CK, and HCC cancer stem cell (CSC) markers (CD133, CD90, CD44) as potential biomarkers for HCC patients. Patients and Methods. This study was conducted on the peripheral blood lymphocytes (PBL) of one 130 participants involving 70 patients with HCC, thirteen patients with chronic hepatitis (CH) and 30 normal controls. For those patients, serum AFP was tested by ELISA. Telomerase, MAGE 1, and MAGE 3, CD90 and CD44 RNA expression was detected by qualitative reverse transcriptase-polymerase chain reaction (qPCR). CD133 and CK expression was measured by flowcytometry (FCM) and qPCR analysis in 10 ml of PBL of each patient. Results. All CH and HCC patients were positive for HCV antibodies. The number of cells expressing CD 133 in the patients PBL was significantly lower in HCC patients than other groups while that of CD90 and CD44 was significantly higher in HCC than in the other groups (p Conclusion. 1) AFP, MAGE1, MAGE 3 and the number of cells expressing CK in the PBL of HCC could be used as markers for early detection of HCC. 2) The CSC markers (CD90, CD44) and AFP are highly expressed in HCC and contribute to aggressive phenotype thus they could be used as prognostic and predictive markers. Citation Format: Abdel-Rahman N. Zekri, Abeer Bahnassy. Evaluation of Alpha-fetoprotein (AFP), telomerase, melanoma associated Antigen (MAGE1 and MAGE 3), cancer stem cell markers cytokeratin (CK) and (CD133,) as potential biomarkers for hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3540. doi:10.1158/1538-7445.AM2013-3540

  • abstract 3540 evaluation of alpha fetoprotein afp telomerase melanoma associated Antigen mage1 and mage 3 cancer stem cell markers cytokeratin ck and cd133 as potential biomarkers for hepatocellular carcinoma hcc
    Cancer Research, 2013
    Co-Authors: Abdelrahman N Zekri, Abeer A Bahnassy
    Abstract:

    Background. Hepatocellular carcinoma (HCC) had been recently classified as a complex disease with a wide range of risk factors. Analysis of AFP level as a tumor marker is applied in patients with a high risk of developing HCC. However, the lack of AFP sensitivity and specificity has elucidated the need for novel tumor markers. Therefore, the aim of the current study is to assess AFP, MAGE1 and MAGE 3, CK, and HCC cancer stem cell (CSC) markers (CD133, CD90, CD44) as potential biomarkers for HCC patients. Patients and Methods. This study was conducted on the peripheral blood lymphocytes (PBL) of one 130 participants involving 70 patients with HCC, thirteen patients with chronic hepatitis (CH) and 30 normal controls. For those patients, serum AFP was tested by ELISA. Telomerase, MAGE 1, and MAGE 3, CD90 and CD44 RNA expression was detected by qualitative reverse transcriptase-polymerase chain reaction (qPCR). CD133 and CK expression was measured by flowcytometry (FCM) and qPCR analysis in 10 ml of PBL of each patient. Results. All CH and HCC patients were positive for HCV antibodies. The number of cells expressing CD 133 in the patients PBL was significantly lower in HCC patients than other groups while that of CD90 and CD44 was significantly higher in HCC than in the other groups (p Conclusion. 1) AFP, MAGE1, MAGE 3 and the number of cells expressing CK in the PBL of HCC could be used as markers for early detection of HCC. 2) The CSC markers (CD90, CD44) and AFP are highly expressed in HCC and contribute to aggressive phenotype thus they could be used as prognostic and predictive markers. Citation Format: Abdel-Rahman N. Zekri, Abeer Bahnassy. Evaluation of Alpha-fetoprotein (AFP), telomerase, melanoma associated Antigen (MAGE1 and MAGE 3), cancer stem cell markers cytokeratin (CK) and (CD133,) as potential biomarkers for hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3540. doi:10.1158/1538-7445.AM2013-3540

Zhi Jian Chen - One of the best experts on this subject based on the ideXlab platform.

  • kinetics of the immune response and regression of metastatic lesions following development of humoral anti high molecular weight melanoma associated Antigen immunity in three patients with advanced malignant melanoma immunized with mouse antiidiotypi
    Cancer Research, 1994
    Co-Authors: Abraham Mittelman, Zhi Jian Chen, C C Liu, S Hirai, Soldano Ferrone
    Abstract:

    Active specific immunotherapy has been implemented in patients with advanced malignant melanoma, utilizing the mouse antiidiotypic (anti-id) monoclonal antibody (mAb) MK2-23 which bears the internal image of high molecular weight-melanoma associated Antigen (HMW-MAA). In a previous study, development of anti-HMW-MAA immunity in patients with advanced malignant melanoma immunized with anti-id mAb MK2-23 was found to be associated with a statistically significant survival prolongation. Since no Information is available about the relationship between development of immunity and clinical response in patients immunized with anti-id mAb, the present study has characterized the kinetics of the immune response in three patients with advanced malignant melanoma who experienced regression of metastatic lesions following immunization with the anti-id mAb MK2-23. The three patients developed anti-mouse IgG antibodies, anti-anti-id antibodies and anti-HMW-MAA antibodies. The anti-HMW-MAA antibodies are mainly IgG, suggesting that the immune response elicited by anti-id mAb MK2-23 is T-cell dependent. The development of anti-HMW-MAA immunity preceded the reduction in the size of metastatic lesions. This temporal relationship suggests but does not prove that the anti-HMW-MAA immunity elicited by anti-id mAb MK2-23 has a beneficial effect on the clinical course of the disease in patients with malignant melanoma. This finding in conjunction with minor side effects associated with repeated administrations of mouse anti-id mAb MK2-23 suggest that active specific immunotherapy with anti-id mAb which bear the internal image of Melanoma-Associated Antigen represents a viable therapeutic approach to malignant melanoma.

  • human high molecular weight melanoma associated Antigen mimicry by mouse antiidiotypic monoclonal antibody tk7 371
    Cancer Research, 1991
    Co-Authors: Zhi Jian Chen, Hong Yang, Toshiro Kageshita, Soldano Ferrone
    Abstract:

    Since the human high-molecular-weight Melanoma-Associated Antigen (HMW-MAA) represents a useful target to implement active specific immunotherapy with mouse antiidiotypic monoclonal antibody (mAb), the present study is aimed at developing and characterizing mouse antiidiotypic mAbs which bear the mirror image of the determinant defined by the anti-HMW-MAA mAb TP61.5. To this end, a BALB/c mouse was immunized with the syngeneic mAb TP61.5. Screening of the 703 generated hybridomas showed that 13 of them secrete antiidiotypic mAbs which inhibit the binding of the immunizing mAb TP61.5 to melanoma cells by at least 75%. The dose of antiidiotypic mAb required to inhibit by 50% the binding of mAb TP61.5 to melanoma cells ranged between 4 and 200 ng. The 13 antiidiotypic mAbs recognize conformational idiotypes, since they did not react in Western blotting with the heavy and light chain of mAb TP61.5 isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Furthermore, the 13 antiidiotypic mAbs did not react with 23 mAbs which recognize 13 determinants of the HMW-MAA distinct from that defined by mAb TP61.5. Analysis of the 13 antiidiotypic mAbs for their ability to elicit cellular and humoral anti-HMW-MAA immunity showed that only mAb TK7-371 elicited a delayed-type hypersensitivity reaction to HMW-MAA-bearing cells in syngeneic hosts and anti-HMW-MAA antibodies in BALB/c mice and in rabbits. Since rabbits express the HMW-MAA, the present results indicate that the antiidiotypic mAb TK7-371 can induce humoral immunity to self HMW-MAA. Therefore, the antiidiotypic mAb TK7-371 may be an efficacious immunogen to implement active specific immunotherapy in patients with melanoma.

  • human high molecular weight melanoma associated Antigen mimicry by mouse antiidiotypic monoclonal antibody mk2 23 characterization of the immunogenicity in syngeneic hosts
    Journal of Immunology, 1991
    Co-Authors: Zhi Jian Chen, Hong Yang, Soldano Ferrone
    Abstract:

    Previous studies have shown that the mouse antiidiotypic mAb MK2-23 elicited with the syngeneic anti-human high molecular weight Melanoma-Associated Ag (HMW-MAA) mAb 763.74 elicits anti-HMW-MAA antibodies in syngeneic hosts and in patients with melanoma. The present investigation has characterized the fine specificity of antibodies elicited by mAb MK2-23, tested its ability to induce delayed-type hypersensitivity reaction to HMW-MAA-bearing melanoma cells and analyzed the variables that influence the immunogenicity of mAb MK2-23. The anti-HMW-MAA antibodies elicited by mAb MK2-23 recognize the same population of molecules recognized by mAb 763.74, react with the same (or spatially close) determinant(s) and express the idiotopes recognized by mAb MK2-23 in their Ag-combining sites. The antiidiotypic antibodies that bind to HMW-MAA have a lower titer than those that do not. These results in conjunction with those obtained in mice using a suboptimal immunization schedule suggest that the idiotope(s) that mimic(s) the mAb 763.74-defined determinant of the HMW-MAA is less immunogenic than those that do not. mAb MK2-23 induces a delayed-type hypersensitivity reaction to HMW-MAA-bearing melanoma cells. Therefore, mAb MK2-23 represents the first example of mouse antiidiotypic mAb that induces a cellular and humoral immunity to a human tumor-associated Ag (TAA), because the previously described mouse antiidiotypic mAb that bear the mirror image of TAA have been shown to induce only humoral anti-TAA immunity. The immunogenicity of mAb MK2-23 is markedly enhanced by its conjugation to keyhole limpet hemocyanin and its administration with FA. Furthermore, the number of immunizations and the doses of mAb MK2-23 injected influence its immunogenicity, although to a lower extent than conjugation to a carrier and mixing with an adjuvant. The information derived from the present investigation represents a useful background to optimize the immunization schedule with mAb MK2-23 in patients with melanoma.

Heidi Schwarzenbach - One of the best experts on this subject based on the ideXlab platform.

  • circulating cell free cancer testis mage a rna boris rna let 7b and mir 202 in the blood of patients with breast cancer and benign breast diseases
    British Journal of Cancer, 2014
    Co-Authors: Simon A Joosse, Volkmar Muller, Bettina Steinbach, Klaus Pantel, Heidi Schwarzenbach
    Abstract:

    MAGE-A (Melanoma-Associated Antigen-A) are promising targets for specific immunotherapy and their expression may be induced by the epigenetic factor BORIS. To determine their relevance for breast cancer, we quantified the levels of MAGE-A1, -A2, -A3, -A12 and BORIS mRNA, as well as microRNAs let-7b and miR-202 in pre- and postoperative serum of 102 and 34 breast cancer patients, respectively, and in serum of 26 patients with benign breast diseases and 37 healthy women by real-time PCR. The mean follow-up time of the cancer patients was 6.2 years. The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001). In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001). Transfection of breast cancer cells with synthetic microRNAs and their inhibitors showed that let-7b and miR-202 did not affect the protein expression of MAGE-A1. Based on their cancer-specific increase in breast cancer patients, circulating MAGE-A and BORIS mRNAs may be further explored for early detection of breast cancer and monitoring of MAGE-directed immunotherapies. Moreover, serum miR-202 is associated with prognosis.

  • circulating cell free cancer testis mage a rna boris rna let 7b and mir 202 in the blood of patients with breast cancer and benign breast diseases
    British Journal of Cancer, 2014
    Co-Authors: Simon A Joosse, Volkmar Muller, Bettina Steinbach, Klaus Pantel, Heidi Schwarzenbach
    Abstract:

    BACKGROUND: MAGE-A (Melanoma-Associated Antigen-A) are promising targets for specific immunotherapy and their expression may be induced by the epigenetic factor BORIS. METHODS: To determine their relevance for breast cancer, we quantified the levels of MAGE-A1, -A2, -A3, -A12 and BORIS mRNA, as well as microRNAs let-7b and miR-202 in pre- and postoperative serum of 102 and 34 breast cancer patients, respectively, and in serum of 26 patients with benign breast diseases and 37 healthy women by real-time PCR. The mean follow-up time of the cancer patients was 6.2 years. RESULTS: The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001). In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001). Transfection of breast cancer cells with synthetic microRNAs and their inhibitors showed that let-7b and miR-202 did not affect the protein expression of MAGE-A1. CONCLUSIONS: Based on their cancer-specific increase in breast cancer patients, circulating MAGE-A and BORIS mRNAs may be further explored for early detection of breast cancer and monitoring of MAGE-directed immunotherapies. Moreover, serum miR-202 is associated with prognosis.