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Antihypertension drug losartan may improve treatment of ovarian cancer

Medical Xpress | January 15, 2019

A new study from a Massachusetts General Hospital (MGH) research team has found that the hypertension drug losartan, which targets the angiotensin signaling pathway, may improve the effectiveness of chemotherapy agents used to treat ovarian cancer. Previous research from the same team identified a similar effect for losartan in animal models of breast and pancreatic cancer, leading to a phase 2 clinical trial that had promising results against pancreatic cancer.
"We know that solid stress imposed by growing cancer cells and the extracellular matrix molecules they produce can compress blood vessels, reducing the delivery of drugs and oxygen to tumors," says Lei Xu, Ph.D., of the Steele Laboratories for Tumor Biology in the MGH Department of Radiation Oncology, co-senior author of the report published online in PNAS. "The extracellular matrix itself can keep high-molecular-weight drugs from penetrating tumors, and angiotensin signaling contributes to matrix formation. Since levels of an important enzyme in the angiotensin pathway are elevated and associated with poor outcomes in ovarian cancer, we investigated whether the use of losartan to decrease fibrosis could improve outcomes in animal models of ovarian cancer."

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Baylor College of Medicine Human Genome Sequencing Center adopts Olink® Explore HT proteomics platform

Globenewswire | August 09, 2023

Olink Holding AB announced that the Baylor College of Medicine Human Genome Sequencing Center (BCM-HGSC) has selected the Olink Explore platform as a proteomics component of their world-class multiomics offering. Understanding the complex biological mechanisms of human diseases is essential to identifying effective new therapeutic strategies. The addition of Olink proteomic technology enables a more thorough understanding of the intricate connections between genes, proteins, and diseases that will lead to improved diagnostics, targeted therapies and the advancement of precision and personalized medicine. “We are immensely pleased to see the Olink Explore HT platform implemented at one of the world’s leading multiomic research centers,“ said Jon Heimer, CEO, Olink Proteomics. “The massive genomic sequencing and automation capabilities of the BCM-HGSC unlocks a unique opportunity for proteogenomic research at scale. We look forward to seeing our tools applied across a broad spectrum of new therapeutic research fields to enhance the existing knowledge of molecular pathways involved in the development, progression, and outcome of disease.” Other large-scale research programs, like the UK Biobank health study, have demonstrated how Olink Explore enables a more complete understanding of the molecular basis of disease. With the addition of Olink proteomics technology, the BCM-HGSC further strengthens its ability to offer unique multiomics capabilities for large population-scale health studies. “Technology development and the adoption of new methods remains a priority at the HGSC, and we are excited to incorporate Olink’s technology into our portfolio,” said Richard Gibbs, Ph.D. Director, Human Genome Sequencing Center and Wofford Cain Professor of Molecular & Human Genetics, Baylor College of Medicine. “The ability to perform high-throughput proteomics opens many possibilities for current and future studies. This technology provides a natural extension from traditional genomic research by providing data that points to the impact of genetic variation on function. A comprehensive, multiomic approach will be needed to determine the mechanism of action of many genetic diseases and is essential for guiding effective prevention and treatment.” The Olink Explore platform represents the cutting edge in proteomic technology. Olink Explore HT is the company's latest solution for high-throughput proteomics, delivering unmatched specificity, scalability, and simplicity. With a completely reimagined and streamlined workflow, Olink Explore HT allows scientists to accurately measure over 5,300 proteins using only 2µl of sample. By combining Olink PEA technology with an NGS readout of relative protein concentrations each thoroughly validated assay maintains the exceptional standards of specificity and sensitivity that Olink users have come to trust. AboutOlink Proteomics Olink Holding AB is a company dedicated to accelerating proteomics together with the scientific community, across multiple disease areas to enable new discoveries and improve the lives of patients. Olink provides a platform of products and services which are deployed across major pharmaceutical companies and leading clinical and academic institutions to deepen the understanding of real-time human biology and drive 21st century healthcare through actionable and impactful science. The Company was founded in 2016 and is well established across Europe, North America and Asia. Olink is headquartered in Uppsala, Sweden.

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NKGen Biotech, Inc. Announces First Patient Dosed in Phase I Clinical Trial of SNK02, Allogeneic NK Cell Therapy Product Candidate

globenewswire | August 29, 2023

NKGen Biotech, Inc. a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic, and CAR-NK natural killer (“NK”) cell therapies, today announced the first patient has been dosed in a Phase I, multi-center, open-label, dose-escalation study evaluating its cryopreserved investigational allogeneic blood-derived NK cell therapy (“SNK02”). In October 2022, the Food and Drug Administration allowed NKGen’s Phase I SNK02 clinical trial to proceed per its Investigational New Drug application. NKGen previously announced a proposed business combination with Graf Acquisition Corp. IV (NYSE: GFOR.U, GFOR, GFOR.WS). This Phase I clinical trial is evaluating the safety and tolerability of SNK02 in participants with pathologically confirmed solid tumors refractory to standard of care therapy. The study drug, SNK02, will be administered as an intravenous infusion, weekly for eight weeks. SNK02 consists of NK cells isolated from healthy donor peripheral blood mononuclear cells. NKGen’s proprietary allogeneic manufacturing process is technically capable of producing hundreds of thousands of potential doses of NK cell therapies from materials collected from a single donor. Processed SNK02 cells are expected to possess 99% purity and very high receptor expression rates. Its cryopreservation process allows the Company to maintain significant cytotoxicity, potentially making SNK02 an accessible investigational off-the-shelf candidate for clinical trials treating malignancies with an emphasis on solid tumors. “We are excited to have dosed our first patient in the Phase I SNK02 clinical trial in refractory cancer patients with limited treatment options,” said Paul Y. Song, M.D., CEO of NKGen. “SNK02 seeks to be one of the first cryopreserved allogeneic NK cell therapy for solid tumors that does not require lymphodepletion before administration. We believe the lack of lymphodepletion has the potential to better preserve the already fragile immune function of heavily pre-treated cancer patients with advanced disease. If successful, this therapy may lead to better overall synergy in future combination regimens with immune checkpoint inhibitors where a robust T-cell response is needed.” About NKGen NKGen is a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic, and CAR-NK natural killer cell therapies. NKGen is headquartered in Santa Ana, California, USA. About Graf Acquisition Corp. IV (“Graf”) Graf is a blank-check company incorporated as a Delaware corporation and formed for the purpose of effecting a merger, capital stock exchange, asset acquisition, stock purchase, reorganization, or similar business combination with one or more businesses.

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Poseida Therapeutics Announces FDA Clearance of Investigational New Drug Application for P-CD19CD20-ALLO1, an Allogeneic Dual CAR-T Cell Therapy

PRNewswire | July 10, 2023

Poseida Therapeutics, Inc. a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for P-CD19CD20-ALLO1, the Company's first allogeneic dual CAR-T cell product candidate, which targets both CD19 and CD20 antigens for the treatment of relapsed or refractory B-cell malignancies and is being developed in partnership with Roche. "We are pleased to receive IND clearance for P-CD19CD20-ALLO1, our third fully allogeneic CAR-T cell product candidate and the second therapy in our partnership with Roche for hematological malignancies that will enter the clinic. We believe this represents the FDA's first known IND clearance of an allogeneic dual CAR-T therapy targeting CD19 and CD20," said Kristin Yarema, Ph.D., President, Cell Therapy at Poseida. "The dual-targeting approach leverages our proprietary non-viral piggyBac® DNA Delivery System, which enables expression of two fully functional CAR molecules into T cells from healthy donors for the treatment of B-cell malignancies that may have heterogeneous antigen expression. We believe that targeting both CD19 and CD20 has the potential to overcome the limitations of currently available CD19-directed CAR-T products where antigen escape has been observed as an important resistance mechanism. It has been estimated that up to 40% of cases where B-cell malignancies relapse or are refractory to CD19 targeting autologous CAR-T therapy may involve antigen escape. We look forward to dosing the first patients in this study." P-CD19CD20-ALLO1 will be evaluated in a Phase 1 multi-center, open-label, dose-escalation study that will enroll up to 70 adult patients with relapsed or refractory B-cell malignancies. The study will evaluate the safety, tolerability, and preliminary efficacy of P-CD19CD20-ALLO1. After enrollment, patients will receive a chemotherapy-based lymphodepletion regimen followed by administration of P-CD19CD20-ALLO1 allogeneic CAR-T cells. With the P-CD19CD20-ALLO1 IND now cleared, the Company is actively focused on opening clinical sites. About P-CD19CD20-ALLO1 P-CD19CD20-ALLO1 is an allogeneic CAR-T cell therapy product candidate being developed for relapsed or refractory B-cell malignancies in partnership with Roche. P-CD19CD20-ALLO1 expresses two fully functional CAR molecules to target cells that express either CD19 or CD20. The dual targeting approach employed in P-CD19CD20-ALLO1 aims to overcome the antigen escape limitations of CD19-only targeted CAR-T therapies by simultaneously targeting both CD19 and CD20. In addition to the dual targeting, P-CD19CD20-ALLO1 uses a novel CD19 binder that showed greater potency in in vivo preclinical models when compared to the canonical FMC63 Single-chain variable fragment (scFv) binder. P-CD19CD20-ALLO1 is an off-the-shelf CAR-T therapy for which patients do not have to undergo apheresis and wait for the cells to be manufactured, which can potentially overcome the limitation of autologous CAR-T therapies associated with significant manufacturing times. P-CD19CD20-ALLO1 will be studied in multiple B-cell malignancies About Poseida Therapeutics, Inc. Poseida Therapeutics is a clinical-stage biopharmaceutical company advancing differentiated cell and gene therapies with the capacity to cure certain cancers and rare diseases. The Company's pipeline includes allogeneic CAR-T cell therapy product candidates for both solid and liquid tumors as well as in vivo gene therapy product candidates that address patient populations with high unmet medical need. The Company's approach to cell and gene therapies is based on its proprietary genetic editing platforms, including its non-viral piggyBac® DNA Delivery System, Cas-CLOVER™ Site-Specific Gene Editing System and nanoparticle and hybrid gene delivery technologies.

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Baylor College of Medicine Human Genome Sequencing Center adopts Olink® Explore HT proteomics platform

Globenewswire | August 09, 2023

Olink Holding AB announced that the Baylor College of Medicine Human Genome Sequencing Center (BCM-HGSC) has selected the Olink Explore platform as a proteomics component of their world-class multiomics offering. Understanding the complex biological mechanisms of human diseases is essential to identifying effective new therapeutic strategies. The addition of Olink proteomic technology enables a more thorough understanding of the intricate connections between genes, proteins, and diseases that will lead to improved diagnostics, targeted therapies and the advancement of precision and personalized medicine. “We are immensely pleased to see the Olink Explore HT platform implemented at one of the world’s leading multiomic research centers,“ said Jon Heimer, CEO, Olink Proteomics. “The massive genomic sequencing and automation capabilities of the BCM-HGSC unlocks a unique opportunity for proteogenomic research at scale. We look forward to seeing our tools applied across a broad spectrum of new therapeutic research fields to enhance the existing knowledge of molecular pathways involved in the development, progression, and outcome of disease.” Other large-scale research programs, like the UK Biobank health study, have demonstrated how Olink Explore enables a more complete understanding of the molecular basis of disease. With the addition of Olink proteomics technology, the BCM-HGSC further strengthens its ability to offer unique multiomics capabilities for large population-scale health studies. “Technology development and the adoption of new methods remains a priority at the HGSC, and we are excited to incorporate Olink’s technology into our portfolio,” said Richard Gibbs, Ph.D. Director, Human Genome Sequencing Center and Wofford Cain Professor of Molecular & Human Genetics, Baylor College of Medicine. “The ability to perform high-throughput proteomics opens many possibilities for current and future studies. This technology provides a natural extension from traditional genomic research by providing data that points to the impact of genetic variation on function. A comprehensive, multiomic approach will be needed to determine the mechanism of action of many genetic diseases and is essential for guiding effective prevention and treatment.” The Olink Explore platform represents the cutting edge in proteomic technology. Olink Explore HT is the company's latest solution for high-throughput proteomics, delivering unmatched specificity, scalability, and simplicity. With a completely reimagined and streamlined workflow, Olink Explore HT allows scientists to accurately measure over 5,300 proteins using only 2µl of sample. By combining Olink PEA technology with an NGS readout of relative protein concentrations each thoroughly validated assay maintains the exceptional standards of specificity and sensitivity that Olink users have come to trust. AboutOlink Proteomics Olink Holding AB is a company dedicated to accelerating proteomics together with the scientific community, across multiple disease areas to enable new discoveries and improve the lives of patients. Olink provides a platform of products and services which are deployed across major pharmaceutical companies and leading clinical and academic institutions to deepen the understanding of real-time human biology and drive 21st century healthcare through actionable and impactful science. The Company was founded in 2016 and is well established across Europe, North America and Asia. Olink is headquartered in Uppsala, Sweden.

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NKGen Biotech, Inc. Announces First Patient Dosed in Phase I Clinical Trial of SNK02, Allogeneic NK Cell Therapy Product Candidate

globenewswire | August 29, 2023

NKGen Biotech, Inc. a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic, and CAR-NK natural killer (“NK”) cell therapies, today announced the first patient has been dosed in a Phase I, multi-center, open-label, dose-escalation study evaluating its cryopreserved investigational allogeneic blood-derived NK cell therapy (“SNK02”). In October 2022, the Food and Drug Administration allowed NKGen’s Phase I SNK02 clinical trial to proceed per its Investigational New Drug application. NKGen previously announced a proposed business combination with Graf Acquisition Corp. IV (NYSE: GFOR.U, GFOR, GFOR.WS). This Phase I clinical trial is evaluating the safety and tolerability of SNK02 in participants with pathologically confirmed solid tumors refractory to standard of care therapy. The study drug, SNK02, will be administered as an intravenous infusion, weekly for eight weeks. SNK02 consists of NK cells isolated from healthy donor peripheral blood mononuclear cells. NKGen’s proprietary allogeneic manufacturing process is technically capable of producing hundreds of thousands of potential doses of NK cell therapies from materials collected from a single donor. Processed SNK02 cells are expected to possess 99% purity and very high receptor expression rates. Its cryopreservation process allows the Company to maintain significant cytotoxicity, potentially making SNK02 an accessible investigational off-the-shelf candidate for clinical trials treating malignancies with an emphasis on solid tumors. “We are excited to have dosed our first patient in the Phase I SNK02 clinical trial in refractory cancer patients with limited treatment options,” said Paul Y. Song, M.D., CEO of NKGen. “SNK02 seeks to be one of the first cryopreserved allogeneic NK cell therapy for solid tumors that does not require lymphodepletion before administration. We believe the lack of lymphodepletion has the potential to better preserve the already fragile immune function of heavily pre-treated cancer patients with advanced disease. If successful, this therapy may lead to better overall synergy in future combination regimens with immune checkpoint inhibitors where a robust T-cell response is needed.” About NKGen NKGen is a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic, and CAR-NK natural killer cell therapies. NKGen is headquartered in Santa Ana, California, USA. About Graf Acquisition Corp. IV (“Graf”) Graf is a blank-check company incorporated as a Delaware corporation and formed for the purpose of effecting a merger, capital stock exchange, asset acquisition, stock purchase, reorganization, or similar business combination with one or more businesses.

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Poseida Therapeutics Announces FDA Clearance of Investigational New Drug Application for P-CD19CD20-ALLO1, an Allogeneic Dual CAR-T Cell Therapy

PRNewswire | July 10, 2023

Poseida Therapeutics, Inc. a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for P-CD19CD20-ALLO1, the Company's first allogeneic dual CAR-T cell product candidate, which targets both CD19 and CD20 antigens for the treatment of relapsed or refractory B-cell malignancies and is being developed in partnership with Roche. "We are pleased to receive IND clearance for P-CD19CD20-ALLO1, our third fully allogeneic CAR-T cell product candidate and the second therapy in our partnership with Roche for hematological malignancies that will enter the clinic. We believe this represents the FDA's first known IND clearance of an allogeneic dual CAR-T therapy targeting CD19 and CD20," said Kristin Yarema, Ph.D., President, Cell Therapy at Poseida. "The dual-targeting approach leverages our proprietary non-viral piggyBac® DNA Delivery System, which enables expression of two fully functional CAR molecules into T cells from healthy donors for the treatment of B-cell malignancies that may have heterogeneous antigen expression. We believe that targeting both CD19 and CD20 has the potential to overcome the limitations of currently available CD19-directed CAR-T products where antigen escape has been observed as an important resistance mechanism. It has been estimated that up to 40% of cases where B-cell malignancies relapse or are refractory to CD19 targeting autologous CAR-T therapy may involve antigen escape. We look forward to dosing the first patients in this study." P-CD19CD20-ALLO1 will be evaluated in a Phase 1 multi-center, open-label, dose-escalation study that will enroll up to 70 adult patients with relapsed or refractory B-cell malignancies. The study will evaluate the safety, tolerability, and preliminary efficacy of P-CD19CD20-ALLO1. After enrollment, patients will receive a chemotherapy-based lymphodepletion regimen followed by administration of P-CD19CD20-ALLO1 allogeneic CAR-T cells. With the P-CD19CD20-ALLO1 IND now cleared, the Company is actively focused on opening clinical sites. About P-CD19CD20-ALLO1 P-CD19CD20-ALLO1 is an allogeneic CAR-T cell therapy product candidate being developed for relapsed or refractory B-cell malignancies in partnership with Roche. P-CD19CD20-ALLO1 expresses two fully functional CAR molecules to target cells that express either CD19 or CD20. The dual targeting approach employed in P-CD19CD20-ALLO1 aims to overcome the antigen escape limitations of CD19-only targeted CAR-T therapies by simultaneously targeting both CD19 and CD20. In addition to the dual targeting, P-CD19CD20-ALLO1 uses a novel CD19 binder that showed greater potency in in vivo preclinical models when compared to the canonical FMC63 Single-chain variable fragment (scFv) binder. P-CD19CD20-ALLO1 is an off-the-shelf CAR-T therapy for which patients do not have to undergo apheresis and wait for the cells to be manufactured, which can potentially overcome the limitation of autologous CAR-T therapies associated with significant manufacturing times. P-CD19CD20-ALLO1 will be studied in multiple B-cell malignancies About Poseida Therapeutics, Inc. Poseida Therapeutics is a clinical-stage biopharmaceutical company advancing differentiated cell and gene therapies with the capacity to cure certain cancers and rare diseases. The Company's pipeline includes allogeneic CAR-T cell therapy product candidates for both solid and liquid tumors as well as in vivo gene therapy product candidates that address patient populations with high unmet medical need. The Company's approach to cell and gene therapies is based on its proprietary genetic editing platforms, including its non-viral piggyBac® DNA Delivery System, Cas-CLOVER™ Site-Specific Gene Editing System and nanoparticle and hybrid gene delivery technologies.

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