The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Stefania Bellone - One of the best experts on this subject based on the ideXlab platform.
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Cervical carcinomas that overexpress human trophoblast Cell-Surface Marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan
Scientific Reports, 2020Co-Authors: Burak Zeybek, Aranzazu Manzano, Anna Bianchi, Elena Bonazzoli, Stefania Bellone, Natalia Buza, Salvatore Lopez, Emanuele Perrone, Paola Manara, Luca ZammataroAbstract:Human trophoblast Cell-Surface Marker (Trop-2) is a Surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of human epithelial solid tumors. We investigated the efficacy of sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised of a humanized anti- Trop-2 antibody, conjugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer Cell lines and a xenograft model. Trop-2 expression was evaluated in 147 primary cervical tumors by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. For in vitro experiments, two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) Cell lines were used. A Cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models. Out of 147 primary cervical cancers, 113 were squamous Cell carcinomas (SCCs), and 34 were adenocarcinoma/adenosquamous carcinomas. Moderate to strong diffuse staining was seen in 95% (108/113) of SCCs, and 81% (29/34) of adenocarcinoma/adenosquamous cancers on immunohistochemistry. Trop-2 positive Cell lines were highly sensitive to sacituzumab govitecan in vitro , with IC_50 values in the range of 0.18 to 0.26 nM (p = 0.02, and p = 0.04 for CVX-8, and ADX-3, respectively). In xenografts, a significant tumor growth inhibition was seen after twice-weekly intravenous administration of the drug for three weeks (p
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cervical carcinomas that overexpress human trophoblast Cell Surface Marker trop 2 are highly sensitive to the antibody drug conjugate sacituzumab govitecan
Scientific Reports, 2020Co-Authors: Burak Zeybek, Aranzazu Manzano, Anna Bianchi, Elena Bonazzoli, Stefania Bellone, Natalia Buza, Salvatore Lopez, Emanuele Perrone, Pei Hui, Paola ManaraAbstract:Human trophoblast Cell-Surface Marker (Trop-2) is a Surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of human epithelial solid tumors. We investigated the efficacy of sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised of a humanized anti- Trop-2 antibody, conjugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer Cell lines and a xenograft model. Trop-2 expression was evaluated in 147 primary cervical tumors by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. For in vitro experiments, two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) Cell lines were used. A Cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models. Out of 147 primary cervical cancers, 113 were squamous Cell carcinomas (SCCs), and 34 were adenocarcinoma/adenosquamous carcinomas. Moderate to strong diffuse staining was seen in 95% (108/113) of SCCs, and 81% (29/34) of adenocarcinoma/adenosquamous cancers on immunohistochemistry. Trop-2 positive Cell lines were highly sensitive to sacituzumab govitecan in vitro, with IC50 values in the range of 0.18 to 0.26 nM (p = 0.02, and p = 0.04 for CVX-8, and ADX-3, respectively). In xenografts, a significant tumor growth inhibition was seen after twice-weekly intravenous administration of the drug for three weeks (p < 0.0001, and p = 0.001 for sacituzumab govitecan vs naked antibody, and sacituzumab govitecan vs control-ADC, respectively). Overall survival at 90 days was significantly improved in the sacituzumab govitecan group (p = 0.014). In conclusion, sacituzumab govitecan may represent a novel targeted therapy option in cervical cancer patients overexpressing Trop-2.
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cervical carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
American Journal of Obstetrics and Gynecology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Natalia Buza, Emiliano Cocco, Elena Ratner, Danarin Silasi, Masoud Azodi, Peter E Schwartz, Thomas J Rutherford, Sergio PecorelliAbstract:Objective We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, against treatment-refractory cervical cancer. Study Design Trop-2 expression was evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. Sensitivity to hRS7 antibody-dependent Cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also investigated. Results Membrane Trop-2 expression was observed in 8 of 8 (100%) of the cancer samples tested by immunohistochemistry, but not in normal cervix. High messenger RNA expression by real-time polymerase chain reaction and high Trop-2 Surface expression by flow cytometry were detected in 80% of cervical cancers (4 of 5 Cell lines). Although these tumors were resistant to natural killer Cell–dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive Cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6–73.2%). Incubation with IL-2 further increased the level of cytotoxicity against Trop-2-positive tumors. Conclusion hRS7 may represent a novel treatment option for patients with cervical cancer refractory to conventional treatment modalities.
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uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized anti trop 2 monoclonal antibody
Cancer, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Maria De Leon, Alessandro D SantinAbstract:BACKGROUND: Uterine serous papillary carcinoma (USPC) was an aggressive and chemotherapy resistant variant of endometrial cancer. The authors evaluated the expression of human trophoblast-Cell-Surface-Marker (Trop-2) and the potential of hRS7, a humanized anti-Trop-2 monoclonal antibody, as a novel therapeutic strategy against USPC. METHODS: Trop-2 expression was evaluated by immunohistochemistry (IHC) in a total of 23 USPC. Six primary USPC Cell lines were assessed by flow cytometry and real-time polymerase chain reaction (PCR) for Trop-2 expression. Sensitivity to hRS7 (Immunomedics, Inc.) antibody-dependent Cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in standard 5-hour 51Cr-release assays against primary USPC Cell lines. RESULTS: Expression of Trop-2 was found in 15 of 23 (65%) of the tumor tissues tested by IHC and in 50% (3 of 6) of the USPC Cell lines tested by real-time PCR and flow-cytometry (Trop-2 expression in USPC versus normal endometrial Cells; P < .005). USPC Cell lines overexpressing Trop-2, regardless of their intrinsic resistance to natural killer cytotoxicity, were highly sensitive to hRS7-mediated ADCC in vitro (range of killing, 28.2% to 64.4%) (P < .001). Negligible cytotoxicity against USPC was seen in the absence of hRS7 or in the presence of rituximab control antibody (range of killing, 1.1% to 12.4%). Incubation with interleukin-2 (50 IU/mL) in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (P = .008). CONCLUSIONS: Trop-2 was highly expressed in uterine serous carcinoma at mRNA and protein levels. Primary USPC Cell lines are highly sensitivity to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for USPC refractory to standard treatment modalities. Cancer 2011. © 2011 American Cancer Society.
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high grade chemotherapy resistant primary ovarian carcinoma Cell lines overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Gynecologic Oncology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Luisa Carrara, Alessandro D SantinAbstract:Abstract Objective. We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a therapeutic agent against chemotherapy-resistant ovarian disease. Methods. Trop-2 expression was evaluated by immunohistochemistry (IHC) in 50 ovarian serous papillary carcinoma specimens. Trop-2 expression was also evaluated by real-time PCR (qRT-PCR) and flow cytometry in a total of 6 primary ovarian cancer Cell lines derived from patients with chemotherapy-resistant disease. Sensitivity to hRS7 antibody-dependent Cellular cytotoxicity (ADCC) was tested in standard 5-hour 51 Cr-release assays. The effect of serum and interleukin-2 (IL-2) on hRS7-mediated ADCC was also studied. Results. Trop-2 expression was found in 41 of 50 (82%) tumor tissues tested by IHC. 83% (5 of 6) of the ovarian cancer Cell lines tested by qRT-PCR and flow cytometry demonstrated high Trop-2 expression. All primary ovarian cancer Cell lines expressing Trop-2 were highly sensitive to hRS7-mediated ADCC in vitro (range of killing: 19.3% to 40.8%) ( p p =0.04). Conclusions. Trop-2 is highly expressed in chemotherapy-resistant ovarian cancer Cell lines at mRNA and protein levels. Primary ovarian carcinoma Cell lines are highly sensitive to hRS7-mediated cytotoxicity in vitro . hRS7 may represent a novel therapeutic agent for the treatment of high-grade, chemotherapy-resistant ovarian cancer.
Alessandro D Santin - One of the best experts on this subject based on the ideXlab platform.
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uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized anti trop 2 monoclonal antibody
Cancer, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Maria De Leon, Alessandro D SantinAbstract:BACKGROUND: Uterine serous papillary carcinoma (USPC) was an aggressive and chemotherapy resistant variant of endometrial cancer. The authors evaluated the expression of human trophoblast-Cell-Surface-Marker (Trop-2) and the potential of hRS7, a humanized anti-Trop-2 monoclonal antibody, as a novel therapeutic strategy against USPC. METHODS: Trop-2 expression was evaluated by immunohistochemistry (IHC) in a total of 23 USPC. Six primary USPC Cell lines were assessed by flow cytometry and real-time polymerase chain reaction (PCR) for Trop-2 expression. Sensitivity to hRS7 (Immunomedics, Inc.) antibody-dependent Cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in standard 5-hour 51Cr-release assays against primary USPC Cell lines. RESULTS: Expression of Trop-2 was found in 15 of 23 (65%) of the tumor tissues tested by IHC and in 50% (3 of 6) of the USPC Cell lines tested by real-time PCR and flow-cytometry (Trop-2 expression in USPC versus normal endometrial Cells; P < .005). USPC Cell lines overexpressing Trop-2, regardless of their intrinsic resistance to natural killer cytotoxicity, were highly sensitive to hRS7-mediated ADCC in vitro (range of killing, 28.2% to 64.4%) (P < .001). Negligible cytotoxicity against USPC was seen in the absence of hRS7 or in the presence of rituximab control antibody (range of killing, 1.1% to 12.4%). Incubation with interleukin-2 (50 IU/mL) in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (P = .008). CONCLUSIONS: Trop-2 was highly expressed in uterine serous carcinoma at mRNA and protein levels. Primary USPC Cell lines are highly sensitivity to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for USPC refractory to standard treatment modalities. Cancer 2011. © 2011 American Cancer Society.
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high grade chemotherapy resistant primary ovarian carcinoma Cell lines overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Gynecologic Oncology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Luisa Carrara, Alessandro D SantinAbstract:Abstract Objective. We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a therapeutic agent against chemotherapy-resistant ovarian disease. Methods. Trop-2 expression was evaluated by immunohistochemistry (IHC) in 50 ovarian serous papillary carcinoma specimens. Trop-2 expression was also evaluated by real-time PCR (qRT-PCR) and flow cytometry in a total of 6 primary ovarian cancer Cell lines derived from patients with chemotherapy-resistant disease. Sensitivity to hRS7 antibody-dependent Cellular cytotoxicity (ADCC) was tested in standard 5-hour 51 Cr-release assays. The effect of serum and interleukin-2 (IL-2) on hRS7-mediated ADCC was also studied. Results. Trop-2 expression was found in 41 of 50 (82%) tumor tissues tested by IHC. 83% (5 of 6) of the ovarian cancer Cell lines tested by qRT-PCR and flow cytometry demonstrated high Trop-2 expression. All primary ovarian cancer Cell lines expressing Trop-2 were highly sensitive to hRS7-mediated ADCC in vitro (range of killing: 19.3% to 40.8%) ( p p =0.04). Conclusions. Trop-2 is highly expressed in chemotherapy-resistant ovarian cancer Cell lines at mRNA and protein levels. Primary ovarian carcinoma Cell lines are highly sensitive to hRS7-mediated cytotoxicity in vitro . hRS7 may represent a novel therapeutic agent for the treatment of high-grade, chemotherapy-resistant ovarian cancer.
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abstract 699 uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Cancer Research, 2010Co-Authors: Alessandro D Santin, Stefania Bellone, Joyce Varughese, Emiliano Cocco, Marta Bellone, Paola Todeschini, Christine E Richter, Francesca Casagrande, K Elsahwi, Danarin SilasiAbstract:Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Purpose: To evaluate the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a novel therapeutic strategy against Uterine Serous Papillary Carcinoma (USPC), a biologically aggressive and chemotherapy resistant variant of endometrial cancer. Methods: Trop-2 expression was evaluated by real time-PCR and flow cytometry in six primary uterine serous papillary carcinoma Cell lines recently characterized in our laboratory. Sensitivity to hRS7 antibody-dependent-Cellular-cytotoxicity (ADCC) was tested in standard 5-hrs 51Cr release-assays against primary USPC Cell lines expressing different levels of Trop-2. Finally, to investigate the effect of interleukin-2 (IL-2) on hRS7-mediated ADCC, 5-hrs 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50-100 IU/ml). Results: Trop-2 mRNA transcript was significantly overexpressed in 3 out of 6 USPC primary Cell lines when compared to normal human endometrial-Cells (NEC) [p=0.005]. Consistent with RT-PCR data, high Surface expression of Trop-2 was detected by flow cytometry in Trop-2 overexpressing Cell lines [i.e., percentage of positive Cells = 100% in all 3 positive Cell lines, median (minimum-maximum) MFI (mean fluorescence intensity) of 184.2 (62.5-276.2)]. Importantly, while these USPC Cell lines were found highly resistant to natural killer dependent cytotoxicity in the absence of the hRS7 antibody (range of killing 1.1% to 12.4%), they showed high sensitivity to hRS7-mediated ADCC in vitro (range of killing 28.2% to 64.4%) (P< 0.001). Incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (p= 0.01). Conclusion: Primary USPC Cell lines may overexpress Trop-2 at mRNA and protein level and are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel, potentially highly effective therapeutic strategy in patients harbouring advanced, recurrent or metastatic USPC refractory to standard treatment modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 699.
Joyce Varughese - One of the best experts on this subject based on the ideXlab platform.
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cervical carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
American Journal of Obstetrics and Gynecology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Natalia Buza, Emiliano Cocco, Elena Ratner, Danarin Silasi, Masoud Azodi, Peter E Schwartz, Thomas J Rutherford, Sergio PecorelliAbstract:Objective We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, against treatment-refractory cervical cancer. Study Design Trop-2 expression was evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. Sensitivity to hRS7 antibody-dependent Cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also investigated. Results Membrane Trop-2 expression was observed in 8 of 8 (100%) of the cancer samples tested by immunohistochemistry, but not in normal cervix. High messenger RNA expression by real-time polymerase chain reaction and high Trop-2 Surface expression by flow cytometry were detected in 80% of cervical cancers (4 of 5 Cell lines). Although these tumors were resistant to natural killer Cell–dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive Cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6–73.2%). Incubation with IL-2 further increased the level of cytotoxicity against Trop-2-positive tumors. Conclusion hRS7 may represent a novel treatment option for patients with cervical cancer refractory to conventional treatment modalities.
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uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized anti trop 2 monoclonal antibody
Cancer, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Maria De Leon, Alessandro D SantinAbstract:BACKGROUND: Uterine serous papillary carcinoma (USPC) was an aggressive and chemotherapy resistant variant of endometrial cancer. The authors evaluated the expression of human trophoblast-Cell-Surface-Marker (Trop-2) and the potential of hRS7, a humanized anti-Trop-2 monoclonal antibody, as a novel therapeutic strategy against USPC. METHODS: Trop-2 expression was evaluated by immunohistochemistry (IHC) in a total of 23 USPC. Six primary USPC Cell lines were assessed by flow cytometry and real-time polymerase chain reaction (PCR) for Trop-2 expression. Sensitivity to hRS7 (Immunomedics, Inc.) antibody-dependent Cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in standard 5-hour 51Cr-release assays against primary USPC Cell lines. RESULTS: Expression of Trop-2 was found in 15 of 23 (65%) of the tumor tissues tested by IHC and in 50% (3 of 6) of the USPC Cell lines tested by real-time PCR and flow-cytometry (Trop-2 expression in USPC versus normal endometrial Cells; P < .005). USPC Cell lines overexpressing Trop-2, regardless of their intrinsic resistance to natural killer cytotoxicity, were highly sensitive to hRS7-mediated ADCC in vitro (range of killing, 28.2% to 64.4%) (P < .001). Negligible cytotoxicity against USPC was seen in the absence of hRS7 or in the presence of rituximab control antibody (range of killing, 1.1% to 12.4%). Incubation with interleukin-2 (50 IU/mL) in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (P = .008). CONCLUSIONS: Trop-2 was highly expressed in uterine serous carcinoma at mRNA and protein levels. Primary USPC Cell lines are highly sensitivity to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for USPC refractory to standard treatment modalities. Cancer 2011. © 2011 American Cancer Society.
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high grade chemotherapy resistant primary ovarian carcinoma Cell lines overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Gynecologic Oncology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Luisa Carrara, Alessandro D SantinAbstract:Abstract Objective. We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a therapeutic agent against chemotherapy-resistant ovarian disease. Methods. Trop-2 expression was evaluated by immunohistochemistry (IHC) in 50 ovarian serous papillary carcinoma specimens. Trop-2 expression was also evaluated by real-time PCR (qRT-PCR) and flow cytometry in a total of 6 primary ovarian cancer Cell lines derived from patients with chemotherapy-resistant disease. Sensitivity to hRS7 antibody-dependent Cellular cytotoxicity (ADCC) was tested in standard 5-hour 51 Cr-release assays. The effect of serum and interleukin-2 (IL-2) on hRS7-mediated ADCC was also studied. Results. Trop-2 expression was found in 41 of 50 (82%) tumor tissues tested by IHC. 83% (5 of 6) of the ovarian cancer Cell lines tested by qRT-PCR and flow cytometry demonstrated high Trop-2 expression. All primary ovarian cancer Cell lines expressing Trop-2 were highly sensitive to hRS7-mediated ADCC in vitro (range of killing: 19.3% to 40.8%) ( p p =0.04). Conclusions. Trop-2 is highly expressed in chemotherapy-resistant ovarian cancer Cell lines at mRNA and protein levels. Primary ovarian carcinoma Cell lines are highly sensitive to hRS7-mediated cytotoxicity in vitro . hRS7 may represent a novel therapeutic agent for the treatment of high-grade, chemotherapy-resistant ovarian cancer.
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abstract 699 uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Cancer Research, 2010Co-Authors: Alessandro D Santin, Stefania Bellone, Joyce Varughese, Emiliano Cocco, Marta Bellone, Paola Todeschini, Christine E Richter, Francesca Casagrande, K Elsahwi, Danarin SilasiAbstract:Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Purpose: To evaluate the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a novel therapeutic strategy against Uterine Serous Papillary Carcinoma (USPC), a biologically aggressive and chemotherapy resistant variant of endometrial cancer. Methods: Trop-2 expression was evaluated by real time-PCR and flow cytometry in six primary uterine serous papillary carcinoma Cell lines recently characterized in our laboratory. Sensitivity to hRS7 antibody-dependent-Cellular-cytotoxicity (ADCC) was tested in standard 5-hrs 51Cr release-assays against primary USPC Cell lines expressing different levels of Trop-2. Finally, to investigate the effect of interleukin-2 (IL-2) on hRS7-mediated ADCC, 5-hrs 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50-100 IU/ml). Results: Trop-2 mRNA transcript was significantly overexpressed in 3 out of 6 USPC primary Cell lines when compared to normal human endometrial-Cells (NEC) [p=0.005]. Consistent with RT-PCR data, high Surface expression of Trop-2 was detected by flow cytometry in Trop-2 overexpressing Cell lines [i.e., percentage of positive Cells = 100% in all 3 positive Cell lines, median (minimum-maximum) MFI (mean fluorescence intensity) of 184.2 (62.5-276.2)]. Importantly, while these USPC Cell lines were found highly resistant to natural killer dependent cytotoxicity in the absence of the hRS7 antibody (range of killing 1.1% to 12.4%), they showed high sensitivity to hRS7-mediated ADCC in vitro (range of killing 28.2% to 64.4%) (P< 0.001). Incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (p= 0.01). Conclusion: Primary USPC Cell lines may overexpress Trop-2 at mRNA and protein level and are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel, potentially highly effective therapeutic strategy in patients harbouring advanced, recurrent or metastatic USPC refractory to standard treatment modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 699.
Emiliano Cocco - One of the best experts on this subject based on the ideXlab platform.
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cervical carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
American Journal of Obstetrics and Gynecology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Natalia Buza, Emiliano Cocco, Elena Ratner, Danarin Silasi, Masoud Azodi, Peter E Schwartz, Thomas J Rutherford, Sergio PecorelliAbstract:Objective We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, against treatment-refractory cervical cancer. Study Design Trop-2 expression was evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. Sensitivity to hRS7 antibody-dependent Cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also investigated. Results Membrane Trop-2 expression was observed in 8 of 8 (100%) of the cancer samples tested by immunohistochemistry, but not in normal cervix. High messenger RNA expression by real-time polymerase chain reaction and high Trop-2 Surface expression by flow cytometry were detected in 80% of cervical cancers (4 of 5 Cell lines). Although these tumors were resistant to natural killer Cell–dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive Cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6–73.2%). Incubation with IL-2 further increased the level of cytotoxicity against Trop-2-positive tumors. Conclusion hRS7 may represent a novel treatment option for patients with cervical cancer refractory to conventional treatment modalities.
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uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized anti trop 2 monoclonal antibody
Cancer, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Maria De Leon, Alessandro D SantinAbstract:BACKGROUND: Uterine serous papillary carcinoma (USPC) was an aggressive and chemotherapy resistant variant of endometrial cancer. The authors evaluated the expression of human trophoblast-Cell-Surface-Marker (Trop-2) and the potential of hRS7, a humanized anti-Trop-2 monoclonal antibody, as a novel therapeutic strategy against USPC. METHODS: Trop-2 expression was evaluated by immunohistochemistry (IHC) in a total of 23 USPC. Six primary USPC Cell lines were assessed by flow cytometry and real-time polymerase chain reaction (PCR) for Trop-2 expression. Sensitivity to hRS7 (Immunomedics, Inc.) antibody-dependent Cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in standard 5-hour 51Cr-release assays against primary USPC Cell lines. RESULTS: Expression of Trop-2 was found in 15 of 23 (65%) of the tumor tissues tested by IHC and in 50% (3 of 6) of the USPC Cell lines tested by real-time PCR and flow-cytometry (Trop-2 expression in USPC versus normal endometrial Cells; P < .005). USPC Cell lines overexpressing Trop-2, regardless of their intrinsic resistance to natural killer cytotoxicity, were highly sensitive to hRS7-mediated ADCC in vitro (range of killing, 28.2% to 64.4%) (P < .001). Negligible cytotoxicity against USPC was seen in the absence of hRS7 or in the presence of rituximab control antibody (range of killing, 1.1% to 12.4%). Incubation with interleukin-2 (50 IU/mL) in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (P = .008). CONCLUSIONS: Trop-2 was highly expressed in uterine serous carcinoma at mRNA and protein levels. Primary USPC Cell lines are highly sensitivity to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for USPC refractory to standard treatment modalities. Cancer 2011. © 2011 American Cancer Society.
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high grade chemotherapy resistant primary ovarian carcinoma Cell lines overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Gynecologic Oncology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Emiliano Cocco, Peter E Schwartz, Thomas J Rutherford, Sergio Pecorelli, Marta Bellone, Paola Todeschini, Luisa Carrara, Alessandro D SantinAbstract:Abstract Objective. We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a therapeutic agent against chemotherapy-resistant ovarian disease. Methods. Trop-2 expression was evaluated by immunohistochemistry (IHC) in 50 ovarian serous papillary carcinoma specimens. Trop-2 expression was also evaluated by real-time PCR (qRT-PCR) and flow cytometry in a total of 6 primary ovarian cancer Cell lines derived from patients with chemotherapy-resistant disease. Sensitivity to hRS7 antibody-dependent Cellular cytotoxicity (ADCC) was tested in standard 5-hour 51 Cr-release assays. The effect of serum and interleukin-2 (IL-2) on hRS7-mediated ADCC was also studied. Results. Trop-2 expression was found in 41 of 50 (82%) tumor tissues tested by IHC. 83% (5 of 6) of the ovarian cancer Cell lines tested by qRT-PCR and flow cytometry demonstrated high Trop-2 expression. All primary ovarian cancer Cell lines expressing Trop-2 were highly sensitive to hRS7-mediated ADCC in vitro (range of killing: 19.3% to 40.8%) ( p p =0.04). Conclusions. Trop-2 is highly expressed in chemotherapy-resistant ovarian cancer Cell lines at mRNA and protein levels. Primary ovarian carcinoma Cell lines are highly sensitive to hRS7-mediated cytotoxicity in vitro . hRS7 may represent a novel therapeutic agent for the treatment of high-grade, chemotherapy-resistant ovarian cancer.
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abstract 699 uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Cancer Research, 2010Co-Authors: Alessandro D Santin, Stefania Bellone, Joyce Varughese, Emiliano Cocco, Marta Bellone, Paola Todeschini, Christine E Richter, Francesca Casagrande, K Elsahwi, Danarin SilasiAbstract:Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Purpose: To evaluate the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a novel therapeutic strategy against Uterine Serous Papillary Carcinoma (USPC), a biologically aggressive and chemotherapy resistant variant of endometrial cancer. Methods: Trop-2 expression was evaluated by real time-PCR and flow cytometry in six primary uterine serous papillary carcinoma Cell lines recently characterized in our laboratory. Sensitivity to hRS7 antibody-dependent-Cellular-cytotoxicity (ADCC) was tested in standard 5-hrs 51Cr release-assays against primary USPC Cell lines expressing different levels of Trop-2. Finally, to investigate the effect of interleukin-2 (IL-2) on hRS7-mediated ADCC, 5-hrs 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50-100 IU/ml). Results: Trop-2 mRNA transcript was significantly overexpressed in 3 out of 6 USPC primary Cell lines when compared to normal human endometrial-Cells (NEC) [p=0.005]. Consistent with RT-PCR data, high Surface expression of Trop-2 was detected by flow cytometry in Trop-2 overexpressing Cell lines [i.e., percentage of positive Cells = 100% in all 3 positive Cell lines, median (minimum-maximum) MFI (mean fluorescence intensity) of 184.2 (62.5-276.2)]. Importantly, while these USPC Cell lines were found highly resistant to natural killer dependent cytotoxicity in the absence of the hRS7 antibody (range of killing 1.1% to 12.4%), they showed high sensitivity to hRS7-mediated ADCC in vitro (range of killing 28.2% to 64.4%) (P< 0.001). Incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (p= 0.01). Conclusion: Primary USPC Cell lines may overexpress Trop-2 at mRNA and protein level and are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel, potentially highly effective therapeutic strategy in patients harbouring advanced, recurrent or metastatic USPC refractory to standard treatment modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 699.
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cervical carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
American Journal of Obstetrics and Gynecology, 2011Co-Authors: Joyce Varughese, Stefania Bellone, Natalia Buza, Emiliano Cocco, Elena Ratner, Danarin Silasi, Masoud Azodi, Peter E Schwartz, Thomas J Rutherford, Sergio PecorelliAbstract:Objective We evaluated the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, against treatment-refractory cervical cancer. Study Design Trop-2 expression was evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. Sensitivity to hRS7 antibody-dependent Cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also investigated. Results Membrane Trop-2 expression was observed in 8 of 8 (100%) of the cancer samples tested by immunohistochemistry, but not in normal cervix. High messenger RNA expression by real-time polymerase chain reaction and high Trop-2 Surface expression by flow cytometry were detected in 80% of cervical cancers (4 of 5 Cell lines). Although these tumors were resistant to natural killer Cell–dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive Cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6–73.2%). Incubation with IL-2 further increased the level of cytotoxicity against Trop-2-positive tumors. Conclusion hRS7 may represent a novel treatment option for patients with cervical cancer refractory to conventional treatment modalities.
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abstract 699 uterine serous papillary carcinomas overexpress human trophoblast Cell Surface Marker trop 2 and are highly sensitive to immunotherapy with hrs7 a humanized monoclonal anti trop 2 antibody
Cancer Research, 2010Co-Authors: Alessandro D Santin, Stefania Bellone, Joyce Varughese, Emiliano Cocco, Marta Bellone, Paola Todeschini, Christine E Richter, Francesca Casagrande, K Elsahwi, Danarin SilasiAbstract:Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Purpose: To evaluate the expression of human trophoblast Cell-Surface Marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a novel therapeutic strategy against Uterine Serous Papillary Carcinoma (USPC), a biologically aggressive and chemotherapy resistant variant of endometrial cancer. Methods: Trop-2 expression was evaluated by real time-PCR and flow cytometry in six primary uterine serous papillary carcinoma Cell lines recently characterized in our laboratory. Sensitivity to hRS7 antibody-dependent-Cellular-cytotoxicity (ADCC) was tested in standard 5-hrs 51Cr release-assays against primary USPC Cell lines expressing different levels of Trop-2. Finally, to investigate the effect of interleukin-2 (IL-2) on hRS7-mediated ADCC, 5-hrs 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50-100 IU/ml). Results: Trop-2 mRNA transcript was significantly overexpressed in 3 out of 6 USPC primary Cell lines when compared to normal human endometrial-Cells (NEC) [p=0.005]. Consistent with RT-PCR data, high Surface expression of Trop-2 was detected by flow cytometry in Trop-2 overexpressing Cell lines [i.e., percentage of positive Cells = 100% in all 3 positive Cell lines, median (minimum-maximum) MFI (mean fluorescence intensity) of 184.2 (62.5-276.2)]. Importantly, while these USPC Cell lines were found highly resistant to natural killer dependent cytotoxicity in the absence of the hRS7 antibody (range of killing 1.1% to 12.4%), they showed high sensitivity to hRS7-mediated ADCC in vitro (range of killing 28.2% to 64.4%) (P< 0.001). Incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity against USPC Cell lines overexpressing Trop-2 (p= 0.01). Conclusion: Primary USPC Cell lines may overexpress Trop-2 at mRNA and protein level and are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel, potentially highly effective therapeutic strategy in patients harbouring advanced, recurrent or metastatic USPC refractory to standard treatment modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 699.