The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
E. Gabriela Chiorean - One of the best experts on this subject based on the ideXlab platform.
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ALgenpantuceL-L immunotherapy in pancreatic adenocarcinoma.
Immunotherapy, 2016Co-Authors: Andrew L. Coveler, Gabriela R. Rossi, Nicholas N. Vahanian, Charles J. Link, E. Gabriela ChioreanAbstract:Pancreatic adenocarcinoma is the 4th Leading cause of cancer death in the USA and the EU. A minority of patients presents with surgicaLLy resectabLe and potentiaLLy curabLe disease, but among these, 80% are destined to reLapse and overaLL survivaL rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potentiaL paradigm shift in the treatment of patients with pancreatic cancer, and may be particuLarLy effective when used earLy in the disease course to prevent metastatic spread. ALgenpantuceL-L (HyperAcute™ Pancreas, NewLink Genetics, Ames, IA, USA) is a whoLe-ceLL immunotherapy consisting of irradiated aLLogeneic pancreatic cancer ceLLs geneticaLLy engineered to express the murine enzyme α-GT, which resuLts in hyperacute rejection of the tumor ceLLs with compLement- and antibody-dependent cytotoxicity. Phase II cLinicaL triaL data has been encouraging, particuLarLy for patients who demonstrated humoraL immunoLogic responses. Here, we report preLiminary re...
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Pancreatic cancer: Update on immunotherapies and ALgenpantuceL-L
Human vaccines & immunotherapeutics, 2015Co-Authors: Kinsey A. Mccormick, Gabriela R. Rossi, Nicholas N. Vahanian, Charles J. Link, Andrew L. Coveler, E. Gabriela ChioreanAbstract:Pancreatic adenocarcinoma is notoriousLy LethaL, and despite improvements in systemic chemotherapy approaches bringing survivaL rates for metastatic disease to aLmost 1 year, by 2030 it is expected to become the second Leading cause of cancer death. Pancreatic cancer (PC) prognosis has been associated with both the presence of intratumoraL heLper and cytotoxic T Lymphocytes, as weLL as humoraL immune responses to tumor associated antigens Like mesotheLin. It is weLL described that the PC microenvironment is characterized by a fibroinfLammatory and immunosuppressive stroma. On these premises severaL immune-targeted strategies have been deveLoped to harness the adaptabLe immune system with a goaL of improving survivaL with LittLe toxicity. Cancer vaccines invoLve the administration of tumor-associated antigens with the goaL of inducing an endogenous anti-tumor response. Among severaL strategies discussed, we wiLL focus on the ALgenpantuceL-L (HyperAcute™ Pancreas) immunotherapy. ALgenpantuceL-L is a whoLe ceLL immunotherapy consisting of irradiated aLLogeneic PC ceLLs geneticaLLy engineered to express the murine enzyme α(1,3)-gaLactosyLtransferase (αGT), which uLtimateLy Leads to hyperacute rejection with compLement- and antibody-dependent cytotoxicity. WhiLe phase III data in the adjuvant treatment of pancreatic cancer are pending, phase II resuLts have been encouraging, particuLarLy for patients who demonstrated humoraL immunoLogic responses. NoveL strategies using immune checkpoint inhibitors, costimuLatory antibodies, and combinations with cancer vaccines may overcome immunotoLerance and improve treatment success.
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CorreLation of anti-caLreticuLin antibody titers with improved overaLL survivaL in a phase 2 cLinicaL triaL of ALgenpantuceL-L immunotherapy for patients with resected pancreatic cancer.
Journal of Clinical Oncology, 2014Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3029 Background: ALgenpantuceL-L immunotherapy consists of aLLogeneic pancreatic cancer ceLLs that have been geneticaLLy modified to express the carbohydrate α(1,3)GaL, to which humans have an inherent pre-existing immunity. It is αGaL that is primariLy responsibLe for the hyperacute rejection of foreign tissue via this potent immune defense mechanism in humans. ALgenpantuceL-L Leverages this mechanism to educate the immune system towards components of the patients’ own tumor ceLLs. CaLreticuLin is a caLcium-binding chaperone protein that functions in the immune response by foLding major histocompatibiLity compLex (MHC) cLass I moLecuLes and infLuencing antigen presentation to cytotoxic T ceLLs. In pre-cLinicaL modeLs, drugs that induce ceLL surface CALR confer enhanced tumor protection. Components of ALgenpantuceL-L express ceLL surface CALR. Methods: An open-LabeL, 71 patient muLticenter phase II study evaLuating ALgenpantuceL-L pLus standard of care gemcitabine with 5-FU-XRT for resected pancreatic can...
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Effect of ALgenpantuceL-L immunotherapy for pancreatic cancer on anti-mesotheLin antibody (Ab) titers and correLation with improved overaLL survivaL.
Journal of Clinical Oncology, 2013Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3007 Background: Hyperacute rejection of tissues expressing the carbohydrate α(1,3)GaL xenoantigen is a potent innate immune defense mechanism that was Leveraged to treat resected pancreatic cancer patients by immunization with geneticaLLy modified aLLogeneic tumor ceLLs expressing αGaL moieties (ALgenpantuceL-L). We propose that adding ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL and induce immunoLogicaL biomarkers that positiveLy correLate with improved median overaLL survivaL (OS). Methods: Open-LabeL, muLticenter phase II study evaLuating ALgenpantuceL-L+SOC (RTOG-9704: gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Endpoints: 1°) disease-free survivaL (DFS) at 1 year; 2°) OS, toxicity and immunoLogic anaLysis. Biomarkers were evaLuated incLuding totaL IgG, compLement, CA19-9 LeveLs, anti-αGaL Ab, anti-CEA Ab, and anti-membrane-bound recombinant mesotheLin (MSLN) Ab. ResuLts: Patients received gemcitabine with 5-FU moduLated radiation therapy pLus ALgenpantuceL-L. The...
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Addition of ALgenpantuceL-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study
Journal of Gastrointestinal Surgery, 2013Co-Authors: Jeffrey M. Hardacre, Jennifer Obel, Howard Safran, William Small, H-j. Lenz, Mary Mulcahy, Mark Talamonti, Smitha Krishnamurthi, Caio S. Rocha-lima, E. Gabriela ChioreanAbstract:Background Despite continued investigation, Limited progress has been made in the adjuvant treatment of resected pancreatic cancer. NoveL or targeted therapies are needed. Methods MuLti-institutionaL, open-LabeL, dose-finding, phase 2 triaL evaLuating the use of ALgenpantuceL-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (CLinicaLTriaLs.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survivaL. Secondary outcomes incLuded overaLL survivaL and toxicity. ResuLts Seventy patients were treated with gemcitabine and 5-fLuorouraciL-based chemoradiotherapy as weLL as ALgenpantuceL-L (mean 12 doses, range 1–14). After a median foLLow-up of 21 months, the 12-month disease-free survivaL was 62 %, and the 12-month overaLL survivaL was 86 %. The most common adverse events were injection site pain and induration. ConcLusions The addition of ALgenpantuceL-L to standard adjuvant therapy for resected pancreatic cancer may improve survivaL. A muLti-institutionaL, phase 3 study is ongoing (CLinicaLTriaLs.gov identifier, NCT01072981).
Jeffrey M. Hardacre - One of the best experts on this subject based on the ideXlab platform.
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CorreLation of anti-caLreticuLin antibody titers with improved overaLL survivaL in a phase 2 cLinicaL triaL of ALgenpantuceL-L immunotherapy for patients with resected pancreatic cancer.
Journal of Clinical Oncology, 2014Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3029 Background: ALgenpantuceL-L immunotherapy consists of aLLogeneic pancreatic cancer ceLLs that have been geneticaLLy modified to express the carbohydrate α(1,3)GaL, to which humans have an inherent pre-existing immunity. It is αGaL that is primariLy responsibLe for the hyperacute rejection of foreign tissue via this potent immune defense mechanism in humans. ALgenpantuceL-L Leverages this mechanism to educate the immune system towards components of the patients’ own tumor ceLLs. CaLreticuLin is a caLcium-binding chaperone protein that functions in the immune response by foLding major histocompatibiLity compLex (MHC) cLass I moLecuLes and infLuencing antigen presentation to cytotoxic T ceLLs. In pre-cLinicaL modeLs, drugs that induce ceLL surface CALR confer enhanced tumor protection. Components of ALgenpantuceL-L express ceLL surface CALR. Methods: An open-LabeL, 71 patient muLticenter phase II study evaLuating ALgenpantuceL-L pLus standard of care gemcitabine with 5-FU-XRT for resected pancreatic can...
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Effect of ALgenpantuceL-L immunotherapy for pancreatic cancer on anti-mesotheLin antibody (Ab) titers and correLation with improved overaLL survivaL.
Journal of Clinical Oncology, 2013Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3007 Background: Hyperacute rejection of tissues expressing the carbohydrate α(1,3)GaL xenoantigen is a potent innate immune defense mechanism that was Leveraged to treat resected pancreatic cancer patients by immunization with geneticaLLy modified aLLogeneic tumor ceLLs expressing αGaL moieties (ALgenpantuceL-L). We propose that adding ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL and induce immunoLogicaL biomarkers that positiveLy correLate with improved median overaLL survivaL (OS). Methods: Open-LabeL, muLticenter phase II study evaLuating ALgenpantuceL-L+SOC (RTOG-9704: gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Endpoints: 1°) disease-free survivaL (DFS) at 1 year; 2°) OS, toxicity and immunoLogic anaLysis. Biomarkers were evaLuated incLuding totaL IgG, compLement, CA19-9 LeveLs, anti-αGaL Ab, anti-CEA Ab, and anti-membrane-bound recombinant mesotheLin (MSLN) Ab. ResuLts: Patients received gemcitabine with 5-FU moduLated radiation therapy pLus ALgenpantuceL-L. The...
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Addition of ALgenpantuceL-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study
Journal of Gastrointestinal Surgery, 2013Co-Authors: Jeffrey M. Hardacre, Jennifer Obel, Howard Safran, William Small, H-j. Lenz, Mary Mulcahy, Mark Talamonti, Smitha Krishnamurthi, Caio S. Rocha-lima, E. Gabriela ChioreanAbstract:Background Despite continued investigation, Limited progress has been made in the adjuvant treatment of resected pancreatic cancer. NoveL or targeted therapies are needed. Methods MuLti-institutionaL, open-LabeL, dose-finding, phase 2 triaL evaLuating the use of ALgenpantuceL-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (CLinicaLTriaLs.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survivaL. Secondary outcomes incLuded overaLL survivaL and toxicity. ResuLts Seventy patients were treated with gemcitabine and 5-fLuorouraciL-based chemoradiotherapy as weLL as ALgenpantuceL-L (mean 12 doses, range 1–14). After a median foLLow-up of 21 months, the 12-month disease-free survivaL was 62 %, and the 12-month overaLL survivaL was 86 %. The most common adverse events were injection site pain and induration. ConcLusions The addition of ALgenpantuceL-L to standard adjuvant therapy for resected pancreatic cancer may improve survivaL. A muLti-institutionaL, phase 3 study is ongoing (CLinicaLTriaLs.gov identifier, NCT01072981).
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Addition of ALgenpantuceL-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: A Phase 2 Study
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2012Co-Authors: Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Howard Safran, William Small, H-j. Lenz, Caio S. Rocha-lima, Smitha S. Krishnamurthi, E. Gabriela ChioreanAbstract:Background Despite continued investigation, Limited progress has been made in the adjuvant treatment of resected pancreatic cancer. NoveL or targeted therapies are needed.
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Addition of ALgenpantuceL-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer.
Journal of Clinical Oncology, 2012Co-Authors: Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, William Small, Nicholas N. VahanianAbstract:4049 Background: Resected pancreatic cancer carries a one year survivaL rate of ~65%. ALgenpantuceL (HyperAcute-Pancreas, HAPa) expLoits the hyperacute rejection mechanism of xenotranspLantation by administering geneticaLLy modified, irradiated, aLLogeneic tumor ceLLs expressing aGaL moieties on their surface. We propose that addition of ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL for patients with resected pancreatic cancer. Methods: Open-LabeL, dose-finding, Phase 2 study (16 sites) evaLuating HAPa (100/300 M ceLLs / dose) + SOC (RTOG-9704: Gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Primary endpoint: 1-year disease-free survivaL (DFS). Secondary Endpoints: overaLL survivaL (OS), toxicity and immunoLogic anaLysis. ResuLts: : 70 patients, median age 62 years, 47% femaLe, 81% Lymph node positive, median tumor size 3.2 cm, and 17% post-operative CA 19-9 ≥ 180 received SOC + HAPa. 1-year DFS of 63% and OS of 86% compares favorabLy to historicaL controLs (~45%% and 65%, ...
Nicholas N. Vahanian - One of the best experts on this subject based on the ideXlab platform.
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ALgenpantuceL-L immunotherapy in pancreatic adenocarcinoma.
Immunotherapy, 2016Co-Authors: Andrew L. Coveler, Gabriela R. Rossi, Nicholas N. Vahanian, Charles J. Link, E. Gabriela ChioreanAbstract:Pancreatic adenocarcinoma is the 4th Leading cause of cancer death in the USA and the EU. A minority of patients presents with surgicaLLy resectabLe and potentiaLLy curabLe disease, but among these, 80% are destined to reLapse and overaLL survivaL rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potentiaL paradigm shift in the treatment of patients with pancreatic cancer, and may be particuLarLy effective when used earLy in the disease course to prevent metastatic spread. ALgenpantuceL-L (HyperAcute™ Pancreas, NewLink Genetics, Ames, IA, USA) is a whoLe-ceLL immunotherapy consisting of irradiated aLLogeneic pancreatic cancer ceLLs geneticaLLy engineered to express the murine enzyme α-GT, which resuLts in hyperacute rejection of the tumor ceLLs with compLement- and antibody-dependent cytotoxicity. Phase II cLinicaL triaL data has been encouraging, particuLarLy for patients who demonstrated humoraL immunoLogic responses. Here, we report preLiminary re...
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Pancreatic cancer: Update on immunotherapies and ALgenpantuceL-L
Human vaccines & immunotherapeutics, 2015Co-Authors: Kinsey A. Mccormick, Gabriela R. Rossi, Nicholas N. Vahanian, Charles J. Link, Andrew L. Coveler, E. Gabriela ChioreanAbstract:Pancreatic adenocarcinoma is notoriousLy LethaL, and despite improvements in systemic chemotherapy approaches bringing survivaL rates for metastatic disease to aLmost 1 year, by 2030 it is expected to become the second Leading cause of cancer death. Pancreatic cancer (PC) prognosis has been associated with both the presence of intratumoraL heLper and cytotoxic T Lymphocytes, as weLL as humoraL immune responses to tumor associated antigens Like mesotheLin. It is weLL described that the PC microenvironment is characterized by a fibroinfLammatory and immunosuppressive stroma. On these premises severaL immune-targeted strategies have been deveLoped to harness the adaptabLe immune system with a goaL of improving survivaL with LittLe toxicity. Cancer vaccines invoLve the administration of tumor-associated antigens with the goaL of inducing an endogenous anti-tumor response. Among severaL strategies discussed, we wiLL focus on the ALgenpantuceL-L (HyperAcute™ Pancreas) immunotherapy. ALgenpantuceL-L is a whoLe ceLL immunotherapy consisting of irradiated aLLogeneic PC ceLLs geneticaLLy engineered to express the murine enzyme α(1,3)-gaLactosyLtransferase (αGT), which uLtimateLy Leads to hyperacute rejection with compLement- and antibody-dependent cytotoxicity. WhiLe phase III data in the adjuvant treatment of pancreatic cancer are pending, phase II resuLts have been encouraging, particuLarLy for patients who demonstrated humoraL immunoLogic responses. NoveL strategies using immune checkpoint inhibitors, costimuLatory antibodies, and combinations with cancer vaccines may overcome immunotoLerance and improve treatment success.
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CorreLation of anti-caLreticuLin antibody titers with improved overaLL survivaL in a phase 2 cLinicaL triaL of ALgenpantuceL-L immunotherapy for patients with resected pancreatic cancer.
Journal of Clinical Oncology, 2014Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3029 Background: ALgenpantuceL-L immunotherapy consists of aLLogeneic pancreatic cancer ceLLs that have been geneticaLLy modified to express the carbohydrate α(1,3)GaL, to which humans have an inherent pre-existing immunity. It is αGaL that is primariLy responsibLe for the hyperacute rejection of foreign tissue via this potent immune defense mechanism in humans. ALgenpantuceL-L Leverages this mechanism to educate the immune system towards components of the patients’ own tumor ceLLs. CaLreticuLin is a caLcium-binding chaperone protein that functions in the immune response by foLding major histocompatibiLity compLex (MHC) cLass I moLecuLes and infLuencing antigen presentation to cytotoxic T ceLLs. In pre-cLinicaL modeLs, drugs that induce ceLL surface CALR confer enhanced tumor protection. Components of ALgenpantuceL-L express ceLL surface CALR. Methods: An open-LabeL, 71 patient muLticenter phase II study evaLuating ALgenpantuceL-L pLus standard of care gemcitabine with 5-FU-XRT for resected pancreatic can...
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Effect of ALgenpantuceL-L immunotherapy for pancreatic cancer on anti-mesotheLin antibody (Ab) titers and correLation with improved overaLL survivaL.
Journal of Clinical Oncology, 2013Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3007 Background: Hyperacute rejection of tissues expressing the carbohydrate α(1,3)GaL xenoantigen is a potent innate immune defense mechanism that was Leveraged to treat resected pancreatic cancer patients by immunization with geneticaLLy modified aLLogeneic tumor ceLLs expressing αGaL moieties (ALgenpantuceL-L). We propose that adding ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL and induce immunoLogicaL biomarkers that positiveLy correLate with improved median overaLL survivaL (OS). Methods: Open-LabeL, muLticenter phase II study evaLuating ALgenpantuceL-L+SOC (RTOG-9704: gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Endpoints: 1°) disease-free survivaL (DFS) at 1 year; 2°) OS, toxicity and immunoLogic anaLysis. Biomarkers were evaLuated incLuding totaL IgG, compLement, CA19-9 LeveLs, anti-αGaL Ab, anti-CEA Ab, and anti-membrane-bound recombinant mesotheLin (MSLN) Ab. ResuLts: Patients received gemcitabine with 5-FU moduLated radiation therapy pLus ALgenpantuceL-L. The...
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Addition of ALgenpantuceL-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer.
Journal of Clinical Oncology, 2012Co-Authors: Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, William Small, Nicholas N. VahanianAbstract:4049 Background: Resected pancreatic cancer carries a one year survivaL rate of ~65%. ALgenpantuceL (HyperAcute-Pancreas, HAPa) expLoits the hyperacute rejection mechanism of xenotranspLantation by administering geneticaLLy modified, irradiated, aLLogeneic tumor ceLLs expressing aGaL moieties on their surface. We propose that addition of ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL for patients with resected pancreatic cancer. Methods: Open-LabeL, dose-finding, Phase 2 study (16 sites) evaLuating HAPa (100/300 M ceLLs / dose) + SOC (RTOG-9704: Gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Primary endpoint: 1-year disease-free survivaL (DFS). Secondary Endpoints: overaLL survivaL (OS), toxicity and immunoLogic anaLysis. ResuLts: : 70 patients, median age 62 years, 47% femaLe, 81% Lymph node positive, median tumor size 3.2 cm, and 17% post-operative CA 19-9 ≥ 180 received SOC + HAPa. 1-year DFS of 63% and OS of 86% compares favorabLy to historicaL controLs (~45%% and 65%, ...
Jennifer Obel - One of the best experts on this subject based on the ideXlab platform.
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CorreLation of anti-caLreticuLin antibody titers with improved overaLL survivaL in a phase 2 cLinicaL triaL of ALgenpantuceL-L immunotherapy for patients with resected pancreatic cancer.
Journal of Clinical Oncology, 2014Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3029 Background: ALgenpantuceL-L immunotherapy consists of aLLogeneic pancreatic cancer ceLLs that have been geneticaLLy modified to express the carbohydrate α(1,3)GaL, to which humans have an inherent pre-existing immunity. It is αGaL that is primariLy responsibLe for the hyperacute rejection of foreign tissue via this potent immune defense mechanism in humans. ALgenpantuceL-L Leverages this mechanism to educate the immune system towards components of the patients’ own tumor ceLLs. CaLreticuLin is a caLcium-binding chaperone protein that functions in the immune response by foLding major histocompatibiLity compLex (MHC) cLass I moLecuLes and infLuencing antigen presentation to cytotoxic T ceLLs. In pre-cLinicaL modeLs, drugs that induce ceLL surface CALR confer enhanced tumor protection. Components of ALgenpantuceL-L express ceLL surface CALR. Methods: An open-LabeL, 71 patient muLticenter phase II study evaLuating ALgenpantuceL-L pLus standard of care gemcitabine with 5-FU-XRT for resected pancreatic can...
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Effect of ALgenpantuceL-L immunotherapy for pancreatic cancer on anti-mesotheLin antibody (Ab) titers and correLation with improved overaLL survivaL.
Journal of Clinical Oncology, 2013Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3007 Background: Hyperacute rejection of tissues expressing the carbohydrate α(1,3)GaL xenoantigen is a potent innate immune defense mechanism that was Leveraged to treat resected pancreatic cancer patients by immunization with geneticaLLy modified aLLogeneic tumor ceLLs expressing αGaL moieties (ALgenpantuceL-L). We propose that adding ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL and induce immunoLogicaL biomarkers that positiveLy correLate with improved median overaLL survivaL (OS). Methods: Open-LabeL, muLticenter phase II study evaLuating ALgenpantuceL-L+SOC (RTOG-9704: gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Endpoints: 1°) disease-free survivaL (DFS) at 1 year; 2°) OS, toxicity and immunoLogic anaLysis. Biomarkers were evaLuated incLuding totaL IgG, compLement, CA19-9 LeveLs, anti-αGaL Ab, anti-CEA Ab, and anti-membrane-bound recombinant mesotheLin (MSLN) Ab. ResuLts: Patients received gemcitabine with 5-FU moduLated radiation therapy pLus ALgenpantuceL-L. The...
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Addition of ALgenpantuceL-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study
Journal of Gastrointestinal Surgery, 2013Co-Authors: Jeffrey M. Hardacre, Jennifer Obel, Howard Safran, William Small, H-j. Lenz, Mary Mulcahy, Mark Talamonti, Smitha Krishnamurthi, Caio S. Rocha-lima, E. Gabriela ChioreanAbstract:Background Despite continued investigation, Limited progress has been made in the adjuvant treatment of resected pancreatic cancer. NoveL or targeted therapies are needed. Methods MuLti-institutionaL, open-LabeL, dose-finding, phase 2 triaL evaLuating the use of ALgenpantuceL-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (CLinicaLTriaLs.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survivaL. Secondary outcomes incLuded overaLL survivaL and toxicity. ResuLts Seventy patients were treated with gemcitabine and 5-fLuorouraciL-based chemoradiotherapy as weLL as ALgenpantuceL-L (mean 12 doses, range 1–14). After a median foLLow-up of 21 months, the 12-month disease-free survivaL was 62 %, and the 12-month overaLL survivaL was 86 %. The most common adverse events were injection site pain and induration. ConcLusions The addition of ALgenpantuceL-L to standard adjuvant therapy for resected pancreatic cancer may improve survivaL. A muLti-institutionaL, phase 3 study is ongoing (CLinicaLTriaLs.gov identifier, NCT01072981).
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Addition of ALgenpantuceL-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: A Phase 2 Study
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2012Co-Authors: Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Howard Safran, William Small, H-j. Lenz, Caio S. Rocha-lima, Smitha S. Krishnamurthi, E. Gabriela ChioreanAbstract:Background Despite continued investigation, Limited progress has been made in the adjuvant treatment of resected pancreatic cancer. NoveL or targeted therapies are needed.
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Addition of ALgenpantuceL-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer.
Journal of Clinical Oncology, 2012Co-Authors: Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, William Small, Nicholas N. VahanianAbstract:4049 Background: Resected pancreatic cancer carries a one year survivaL rate of ~65%. ALgenpantuceL (HyperAcute-Pancreas, HAPa) expLoits the hyperacute rejection mechanism of xenotranspLantation by administering geneticaLLy modified, irradiated, aLLogeneic tumor ceLLs expressing aGaL moieties on their surface. We propose that addition of ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL for patients with resected pancreatic cancer. Methods: Open-LabeL, dose-finding, Phase 2 study (16 sites) evaLuating HAPa (100/300 M ceLLs / dose) + SOC (RTOG-9704: Gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Primary endpoint: 1-year disease-free survivaL (DFS). Secondary Endpoints: overaLL survivaL (OS), toxicity and immunoLogic anaLysis. ResuLts: : 70 patients, median age 62 years, 47% femaLe, 81% Lymph node positive, median tumor size 3.2 cm, and 17% post-operative CA 19-9 ≥ 180 received SOC + HAPa. 1-year DFS of 63% and OS of 86% compares favorabLy to historicaL controLs (~45%% and 65%, ...
Howard Safran - One of the best experts on this subject based on the ideXlab platform.
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CorreLation of anti-caLreticuLin antibody titers with improved overaLL survivaL in a phase 2 cLinicaL triaL of ALgenpantuceL-L immunotherapy for patients with resected pancreatic cancer.
Journal of Clinical Oncology, 2014Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3029 Background: ALgenpantuceL-L immunotherapy consists of aLLogeneic pancreatic cancer ceLLs that have been geneticaLLy modified to express the carbohydrate α(1,3)GaL, to which humans have an inherent pre-existing immunity. It is αGaL that is primariLy responsibLe for the hyperacute rejection of foreign tissue via this potent immune defense mechanism in humans. ALgenpantuceL-L Leverages this mechanism to educate the immune system towards components of the patients’ own tumor ceLLs. CaLreticuLin is a caLcium-binding chaperone protein that functions in the immune response by foLding major histocompatibiLity compLex (MHC) cLass I moLecuLes and infLuencing antigen presentation to cytotoxic T ceLLs. In pre-cLinicaL modeLs, drugs that induce ceLL surface CALR confer enhanced tumor protection. Components of ALgenpantuceL-L express ceLL surface CALR. Methods: An open-LabeL, 71 patient muLticenter phase II study evaLuating ALgenpantuceL-L pLus standard of care gemcitabine with 5-FU-XRT for resected pancreatic can...
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Effect of ALgenpantuceL-L immunotherapy for pancreatic cancer on anti-mesotheLin antibody (Ab) titers and correLation with improved overaLL survivaL.
Journal of Clinical Oncology, 2013Co-Authors: Gabriela R. Rossi, Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, Nicholas N. VahanianAbstract:3007 Background: Hyperacute rejection of tissues expressing the carbohydrate α(1,3)GaL xenoantigen is a potent innate immune defense mechanism that was Leveraged to treat resected pancreatic cancer patients by immunization with geneticaLLy modified aLLogeneic tumor ceLLs expressing αGaL moieties (ALgenpantuceL-L). We propose that adding ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL and induce immunoLogicaL biomarkers that positiveLy correLate with improved median overaLL survivaL (OS). Methods: Open-LabeL, muLticenter phase II study evaLuating ALgenpantuceL-L+SOC (RTOG-9704: gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Endpoints: 1°) disease-free survivaL (DFS) at 1 year; 2°) OS, toxicity and immunoLogic anaLysis. Biomarkers were evaLuated incLuding totaL IgG, compLement, CA19-9 LeveLs, anti-αGaL Ab, anti-CEA Ab, and anti-membrane-bound recombinant mesotheLin (MSLN) Ab. ResuLts: Patients received gemcitabine with 5-FU moduLated radiation therapy pLus ALgenpantuceL-L. The...
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Addition of ALgenpantuceL-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study
Journal of Gastrointestinal Surgery, 2013Co-Authors: Jeffrey M. Hardacre, Jennifer Obel, Howard Safran, William Small, H-j. Lenz, Mary Mulcahy, Mark Talamonti, Smitha Krishnamurthi, Caio S. Rocha-lima, E. Gabriela ChioreanAbstract:Background Despite continued investigation, Limited progress has been made in the adjuvant treatment of resected pancreatic cancer. NoveL or targeted therapies are needed. Methods MuLti-institutionaL, open-LabeL, dose-finding, phase 2 triaL evaLuating the use of ALgenpantuceL-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (CLinicaLTriaLs.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survivaL. Secondary outcomes incLuded overaLL survivaL and toxicity. ResuLts Seventy patients were treated with gemcitabine and 5-fLuorouraciL-based chemoradiotherapy as weLL as ALgenpantuceL-L (mean 12 doses, range 1–14). After a median foLLow-up of 21 months, the 12-month disease-free survivaL was 62 %, and the 12-month overaLL survivaL was 86 %. The most common adverse events were injection site pain and induration. ConcLusions The addition of ALgenpantuceL-L to standard adjuvant therapy for resected pancreatic cancer may improve survivaL. A muLti-institutionaL, phase 3 study is ongoing (CLinicaLTriaLs.gov identifier, NCT01072981).
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Addition of ALgenpantuceL-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: A Phase 2 Study
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2012Co-Authors: Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Howard Safran, William Small, H-j. Lenz, Caio S. Rocha-lima, Smitha S. Krishnamurthi, E. Gabriela ChioreanAbstract:Background Despite continued investigation, Limited progress has been made in the adjuvant treatment of resected pancreatic cancer. NoveL or targeted therapies are needed.
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Addition of ALgenpantuceL-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer.
Journal of Clinical Oncology, 2012Co-Authors: Jeffrey M. Hardacre, Mary F. Mulcahy, Mark S. Talamonti, Jennifer Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-josef Lenz, E. Gabriela Chiorean, William Small, Nicholas N. VahanianAbstract:4049 Background: Resected pancreatic cancer carries a one year survivaL rate of ~65%. ALgenpantuceL (HyperAcute-Pancreas, HAPa) expLoits the hyperacute rejection mechanism of xenotranspLantation by administering geneticaLLy modified, irradiated, aLLogeneic tumor ceLLs expressing aGaL moieties on their surface. We propose that addition of ALgenpantuceL-L to SOC adjuvant therapy may improve survivaL for patients with resected pancreatic cancer. Methods: Open-LabeL, dose-finding, Phase 2 study (16 sites) evaLuating HAPa (100/300 M ceLLs / dose) + SOC (RTOG-9704: Gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Primary endpoint: 1-year disease-free survivaL (DFS). Secondary Endpoints: overaLL survivaL (OS), toxicity and immunoLogic anaLysis. ResuLts: : 70 patients, median age 62 years, 47% femaLe, 81% Lymph node positive, median tumor size 3.2 cm, and 17% post-operative CA 19-9 ≥ 180 received SOC + HAPa. 1-year DFS of 63% and OS of 86% compares favorabLy to historicaL controLs (~45%% and 65%, ...