The Experts below are selected from a list of 119976 Experts worldwide ranked by ideXlab platform
Camelia-maria Monoranu - One of the best experts on this subject based on the ideXlab platform.
-
Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy?
PloS one, 2015Co-Authors: Constantin Lapa, Thomas Linsenmann, Katharina Lückerath, Samuel Samnick, Ken Herrmann, Carolin Stoffer, Ralf-ingo Ernestus, Andreas K. Buck, Mario Löhr, Camelia-maria MonoranuAbstract:BACKGROUND Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM. METHODS 15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry. RESULTS The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns. CONCLUSION SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.
-
tumor associated macrophages in glioblastoma multiforme a Suitable Target for somatostatin receptor based imaging and therapy
PLOS ONE, 2015Co-Authors: Constantin Lapa, Thomas Linsenmann, Katharina Lückerath, Samuel Samnick, Ken Herrmann, Carolin Stoffer, Ralf-ingo Ernestus, Andreas K. Buck, Mario Löhr, Camelia-maria MonoranuAbstract:BACKGROUND Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM. METHODS 15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry. RESULTS The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns. CONCLUSION SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.
Maurizio Chiriva-internati - One of the best experts on this subject based on the ideXlab platform.
-
myeloma Sperm protein 17 (Sp17)is a Suitable Target for immunotherapy of multiple
2013Co-Authors: Maurizio Chiriva-internati, Zhiqing Wang, Emanuela Salati, Klaus Bumm, Bart Barlogie, Seah H. LimAbstract:ABSTRACT Sperm protein 17 (Sp17) is a protein recently identified as a novel cancer-testis (CT) antigen in multiple myeloma (MM). Since this tumor antigen demonstrates a very restricted normal tissue expression, Sp17 may be an excellent Target for tumor vaccine of MM. In this present study, we determined the ability to generate Sp17-specific HLA-class I restricted CTLs from the peripheral blood of 4 patients with MM, 3 consecutive Sp17-positive patients and one Sp17-negative patient. Dendritic cells were generated from monocytes of four patients with MM and used to present a recombinant Sp17 protein to autologous T cells. Following four rounds of antigen stimulation, the CTLs were tested for their ability to kill autologous Targets in an Sp17 dependent and HLA-class I restricted manner in standard cytotoxicity assays. Despite previous chemotherapy and the immunosuppression so often associated with multiple myeloma, CTL generation was successful in all 4 patients, irrespectively of the Sp17 status of their tumors. Most importantly, the CTLs were able to lyse autologous tumor cells that expressed Sp17. Tumor cell lysis in all cases appeared to be mainly perforin-mediated and could be blocked by Concanamycin A. We conclude that Sp17 is a Suitable Target for immunotherapy of multiple myeloma. Our findings provide the basis for a clinical study aimed at inducing a cellular immune response directed at Sp17-positive MM.From bloodjournal.hematologylibrary.org by guest on May 29, 2013. For personal use only.
-
Sperm protein 17 is a Suitable Target for adoptive T-cell-based immunotherapy in human ovarian cancer.
Journal of immunotherapy (Hagerstown Md. : 1997), 2008Co-Authors: Maurizio Chiriva-internati, Jon A. Weidanz, Eldo E. Frezza, Marjorie Jenkins, Ronald C. Kennedy, Everardo Cobos, W. Martin KastAbstract:For ovarian cancer (OC) patients with advanced or metastatic disease, standard treatments (chemotherapy and radiotherapy) are not very effective and have undesirable side effects. Newer and more promising approaches in cancer treatment use components of the immune system. In this study, we applied an adoptive immunotherapy-based approach using a cancer testis antigen, sperm protein 17, as a Target for the treatment of human metastatic OC in a NOD.CB17-PrkDccid/J (nonobese, diabetic severe combined immunodeficient) mouse model. We used the human SK-OV-3A2.A3 OC cell line, endogenously expressing sperm protein 17, to induce tumor growth in mice. We provide direct evidence, for the first time, that in vitro cultured, monoclonal, cytotoxic T lymphocytes (derived either from advanced OC patients or from healthy donors), specific for sperm protein 17, can eradicate human metastatic OC cells. In addition, we observed no evidence of autoimmunity after histologic examination of the tissue sections adding to the safety profile of our approach.
-
Sperm protein 17 (Sp17) is a Suitable Target for immunotherapy of multiple myeloma
Blood, 2002Co-Authors: Maurizio Chiriva-internati, Zhiqing Wang, Emanuela Salati, Klaus Bumm, Bart Barlogie, Seah H. LimAbstract:Sperm protein 17 (Sp17) is a protein recently identified as a novel cancer-testis (CT) antigen in multiple myeloma (MM). Because this tumor antigen demonstrates a very restricted normal tissue expression, Sp17 may be an excellent Target for tumor vaccine of MM. In this study, we determined the ability to generate Sp17-specific HLA class I–restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of 4 patients with MM, 3 consecutive Sp17+patients, and 1 Sp17− patient. Dendritic cells were generated from monocytes of 4 patients with MM and used to present a recombinant Sp17 protein to autologous T cells. Following 4 rounds of antigen stimulation, the CTLs were tested for their ability to kill autologous Targets in an Sp17-dependent and HLA-class I– restricted manner in standard cytotoxicity assays. Despite previous chemotherapy and the immunosuppression so often associated with MM, CTL generation was successful in all 4 patients, irrespective of the Sp17 status of their tumors. Most importantly, the CTLs were able to lyse autologous tumor cells that expressed Sp17. Tumor cell lysis in all cases appeared to be mainly mediated by perforin and could be blocked by concanamycin A. We conclude that Sp17 is a Suitable Target for immunotherapy of MM. Our findings provide the basis for a clinical study aimed at inducing a cellular immune response directed at Sp17+ MM.
Mario Mellado - One of the best experts on this subject based on the ideXlab platform.
-
Chemokine signaling defines novel Targets for therapeutic intervention.
Mini reviews in medicinal chemistry, 2005Co-Authors: José Miguel Rodríguez-frade, Carlos Martínez-a, Mario MelladoAbstract:Members of the human chemokine family are considered a Suitable Target for therapeutic intervention, as they have a fundamental role in several important human diseases. Here we outline potential new areas of intervention based on recent findings on chemokine receptor function.
Constantin Lapa - One of the best experts on this subject based on the ideXlab platform.
-
Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy?
PloS one, 2015Co-Authors: Constantin Lapa, Thomas Linsenmann, Katharina Lückerath, Samuel Samnick, Ken Herrmann, Carolin Stoffer, Ralf-ingo Ernestus, Andreas K. Buck, Mario Löhr, Camelia-maria MonoranuAbstract:BACKGROUND Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM. METHODS 15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry. RESULTS The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns. CONCLUSION SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.
-
tumor associated macrophages in glioblastoma multiforme a Suitable Target for somatostatin receptor based imaging and therapy
PLOS ONE, 2015Co-Authors: Constantin Lapa, Thomas Linsenmann, Katharina Lückerath, Samuel Samnick, Ken Herrmann, Carolin Stoffer, Ralf-ingo Ernestus, Andreas K. Buck, Mario Löhr, Camelia-maria MonoranuAbstract:BACKGROUND Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM. METHODS 15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry. RESULTS The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns. CONCLUSION SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.
W. Martin Kast - One of the best experts on this subject based on the ideXlab platform.
-
Sperm protein 17 is a Suitable Target for adoptive T-cell-based immunotherapy in human ovarian cancer.
Journal of immunotherapy (Hagerstown Md. : 1997), 2008Co-Authors: Maurizio Chiriva-internati, Jon A. Weidanz, Eldo E. Frezza, Marjorie Jenkins, Ronald C. Kennedy, Everardo Cobos, W. Martin KastAbstract:For ovarian cancer (OC) patients with advanced or metastatic disease, standard treatments (chemotherapy and radiotherapy) are not very effective and have undesirable side effects. Newer and more promising approaches in cancer treatment use components of the immune system. In this study, we applied an adoptive immunotherapy-based approach using a cancer testis antigen, sperm protein 17, as a Target for the treatment of human metastatic OC in a NOD.CB17-PrkDccid/J (nonobese, diabetic severe combined immunodeficient) mouse model. We used the human SK-OV-3A2.A3 OC cell line, endogenously expressing sperm protein 17, to induce tumor growth in mice. We provide direct evidence, for the first time, that in vitro cultured, monoclonal, cytotoxic T lymphocytes (derived either from advanced OC patients or from healthy donors), specific for sperm protein 17, can eradicate human metastatic OC cells. In addition, we observed no evidence of autoimmunity after histologic examination of the tissue sections adding to the safety profile of our approach.
