Cade Hildreth, B.A., M.S. - BioInformant’s Post

Stem Cell Therapy developers I Peace and iCamuno Biotherapeutics Start Natural Killer Cell Trial for Ovarian Cancer - https://lnkd.in/ewK_iFg5 I Peace, a pioneering CDMO in induced pluripotent stem (iPS) cells, and iCamuno Biotherapeutics, a biotech company developing iPS cell-based therapies, today announced a significant milestone with the dosing of the first patient in a clinical trial using iPS cell-derived natural killer (iNK) cells for ovarian cancer immunotherapy. iCamuno will lead the trial, which will test the safety and efficacy of NK cells made from I Peace’s cGMP-compliant iPS cells using iCamuno’s NK cell differentiation technology. Natural killer (NK) cells are a critical component of the anti-cancer immune system, with natural abilities to recognize and destroy tumor cells. This trial leverages iCamuno’s abilities to create cGMP-grade iPS cell-derived NK cells with improved consistency and effector function. The initial phase will focus on ovarian cancer, with potential expansion to a broader range of diseases. “We are thrilled to reach this moment,” said Koji Tanabe, CEO and founder at I Peace, Inc.| Cell and Gene Therapy Manufacturing, cGMP iPSCs | CDMO. “Dosing the first patient in this trial using our iPS cell line is a significant milestone in our goal to develop innovative immunotherapies for cancer.” “This is an important milestone for iCamuno,” said Ethan Liu, Chairman and co-founder of iCamuno Biotherapeutics Pty Ltd. “Given their safety and efficacy in preclinical testing, we are hopeful that our iNK cells will be a valuable weapon in the battle against ovarian cancer.” #ipscells #stemcells #nkcells #advancedtherapies

Mesenchymal stem cells in the tumor microenvironment promote bladder cancer progression by modifying cancer cell mitochondrial activity and enhancing energy production In the tumor microenvironment, mesenchymal stem cells (MSCs) are essential for the initiation, development, and metastasis of cancer, although the role and mechanisms of MSCs in bladder cancer remain poorly understood. In a recent article in Cell Death and Disease 15, 688 (2024), Yang et al. analyzed the biological roles and molecular mechanisms of MSCs in bladder cancer cells using samples from 205 patients. They report that a high tumor-stroma ratio is significantly associated with larger tumor size, higher T stage, pathological grade, increased vascular invasion and poorer overall survival. Main points of the study: • The release of tryptophan metabolites (such as kynurenine) by mesenchymal stem cells in the tumor microenvironment may enhance mitochondrial autophagy and biogenesis, thereby increasing energy production in bladder cancer cells. • Mesenchymal stem cells in the tumor microenvironment promote bladder cancer cell proliferation, migration, and invasion in both in vitro and in vivo studies. • These effects can be reversed by inhibiting IDO1 (indoleamine 2,3-dioxygenase 1), an enzyme that reduces tryptophan levels thus increasing its metabolites. https://lnkd.in/d6rD82Cp

Genetically engineering a treatment for incurable brain tumors. Purdue University researchers develop fully off-the-shelf, stem cell-derived, natural killer cells against glioblastoma. April 22, 2024. Excerpt: Purdue University researchers are developing and validating a patent-pending treatment for incurable glioblastoma brain tumors. Glioblastomas are almost always lethal with a median survival of 14 months. Traditional methods used against other cancers, such as chemotherapy and immunotherapy, are often ineffective on glioblastoma. Sandro Matosevic, Associate Professor in the Department of Industrial and Molecular Pharmaceutics in Purdue’s College of Pharmacy, leads a team of researchers developing a novel immunotherapy. Matosevic is also on the faculty of the Purdue Institute for Cancer Research and Purdue Institute for Drug Discovery. The Matosevic-led research has been published in peer-reviewed journal Nature Communications, 01 March 2024. Link accessible in enclosed announcement. Note: “We are developing immunotherapy based on novel, genetically engineered, off-the-shelf or allogeneic immune cells. Allogeneic cells are not sourced from the same patient, but rather another source,” Matosevic said. “In our study, we engineered cells from induced pluripotent stem cells. We eliminated the need for blood and instead differentiated stem cells into immune cells, or natural killer cells, and then genetically engineered those.” Matosevic said novel Purdue immunotherapy can be considered to have a true off-the-shelf source. “We can envision having unlimited supplies of stem cells ready to be engineered,” Matosevic said. “This does not require blood to be sourced. And because these are human cells, they are directly usable in human patients.” The Purdue Innovates Office of Technology Commercialization has applied for a patent from the U.S. Patent and Trademark Office to protect the intellectual property. Inquiries about the status of the intellectual property may be directed to Joe Kasper, assistant director of business development and licensing — life sciences, at jrkasper@prf.org.

New dual stem cell therapy developed to treat brain metastasis in patients with non-small cell lung cancer New research highlights the promise of a novel stem cell treatment strategy for leptomeningeal brain metastasis (LBM), a severe form of metastatic brain cancer that spreads to membranes surrounding the brain and spinal cord and occurs in up to 20% of people with cancer. The researchers say their findings in newly developed preclinical models of metastatic non-small cell lung cancer (NSCLC) support pursuing clinical trials for this treatment strategy. LBM is a severe form of disease that often occurs in those diagnosed with NSCLC, breast cancer and melanoma, and is linked to poor rates of survival, ranging from eight to 10 weeks. While first-line therapies for cancer such as chemotherapy have been shown to be ineffective in treating LBM, immune checkpoint inhibitors (ICIs) often have more success in treating NSCLC brain metastasis. However, the efficacy of ICIs in treating LBM from NSCLC has been less successful. To further investigate this, Mass General Brigham scientists first created immune-competent LBM mouse models that mimic LBM in patient settings. To enhance tumor cell killing and modulate the immune tumor environment, scientists explored testing the therapeutic activity of allogeneic dual stem cells releasing oncolytic herpes simplex virus (oHSV) and a single chain variable fragment of anti-PD-1 (scFvPD-1) in the preclinical models. https://lnkd.in/eswqUY6p https://lnkd.in/eHJtQDQh

Cancer Stem Cell Targeted Therapy Cancer stem cell (CSC) targeted therapy is an advanced approach in oncology that aims to eradicate cancer stem cells, which are believed to play a crucial role in cancer relapse and resistance to conventional treatments. These cells have the ability to self-renew and differentiate, contributing to the heterogeneity and resilience of tumors. By specifically targeting CSCs, this therapy can prevent the growth and spread of cancer, ultimately reducing the likelihood of relapse and improving treatment efficacy. CSC targeted therapy involves a variety of strategies, such as the use of monoclonal antibodies, small molecule inhibitors, and immune-mediated disruption, specifically targeting surface markers or signaling pathways that are critical for CSC survival and proliferation. For example, drugs are currently being investigated that inhibit pathways such as Wnt, Notch, and Hedgehog, which are essential for CSC maintenance and self-renewal. Another promising approach is the use of oncolytic viruses, which are engineered to selectively infect and kill CSCs without harming normal cells. In addition, researchers are exploring the potential of combining CSC targeted therapy with traditional chemotherapy and radiation therapy to achieve more comprehensive eradication of CSCs and non-stem cell cancer cells. Despite its potential, targeting CSCs remains a major challenge due to the similarity of molecular markers on CSCs and normal stem cells, which can lead to toxicity and adverse effects. Ongoing research and clinical trials continue to refine these approaches with the goal of effectively integrating CSC-targeted therapies into standard cancer treatment regimens. References [1] Xianjing Chu et al., Signal Transduction and Targeted Therapy 2024 (https://lnkd.in/e-qqenuM) [2] Liqun Yang et al., Signal Transduction and Targeted Therapy 2020 (https://lnkd.in/en-RiDmM) #CancerStemCells #OncologyInnovation #CSCTherapy #TargetedTherapy #CancerResearch #OncolyticViruses #MonoclonalAntibodies #MedicalScience #FutureOfCancerTreatment #HealthcareTrends

🌟 𝑮𝒐𝒐𝒅 𝑴𝒐𝒓𝒏𝒊𝒏𝒈 𝒘𝒊𝒕𝒉 𝒕𝒉𝒆 𝑯𝒊𝒈𝒉𝒍𝒊𝒈𝒉𝒕𝒔 𝒐𝒇 𝒕𝒉𝒆 𝑾𝒆𝒆𝒌! 🌟 📜 New publication by HI-STEM gGmbH: The Heidelberg Institute for Stem Cell Technology and Experimental Medicine - The study investigates how circulating tumor cells (CTCs) drive metastasis in breast cancer. Due to their low abundance, robust expansion protocols are essential for effective study. This research establishes long-term CTC-derived organoids from metastatic breast cancer patients. Multiomics and preclinical models identified the NRG1–HER3 signaling pathway as crucial for CTC survival, growth, and dissemination. CRISPR screens revealed that FGFR1 signaling compensates for NRG1–HER3 deficiency. Activation of NRG1–HER3 induced resistance to FGFR1 inhibition, while the combined blockade of both pathways impaired CTC growth. This study highlights the dynamic interplay of signaling pathways and offers new strategies for targeting cancer cell plasticity in precision medicine. https://bit.ly/3WqWyl1 Andreas Trumpp, Martin Sprick, Roberto Würth 📜 The recent publication, "Exploration of Novel Biomarkers for Neurodegenerative Diseases Using Proteomic Analysis and Ligand-Binding Assays," is the result of a collaboration between AbbVie and Sciomics, showcasing the power of partnerships between their combined expertise in proteomics and biomarker development. The study investigates innovative biomarkers for neurodegenerative diseases such as Alzheimer’s and Parkinson’s by combining proteomic analysis and ligand-binding assays. Researchers identified proteins like CD14 and osteopontin that were differentially expressed in patient samples, offering significant potential for improving disease diagnosis and monitoring progression. https://bit.ly/40ktBZ9 Dr. Christoph Schröder, Ronny Schmidt, Joachim Vogt   🚀 BioMed X Institute Launches New Collaboration with Daiichi Sankyo Europe GmbH in Cancer Therapy - This new initiative wants to develop next-generation therapies using bi- and multi-specific biologics to target the tumor microenvironment. The aim is to overcome the limitations of conventional treatments by exploring novel target combinations and leveraging synergistic antitumor effects. Key research challenges include the development of innovative therapeutic concepts for bi- or multi-specific biologics that address new extracellular or intracellular target combinations for treating solid tumors, the exploration and functional validation of promising target combinations both in vitro and in vivo, and the creation of sophisticated in vitro assay systems to assess the functionality of these novel target combinations. Applications are invited to form the new research team. https://bit.ly/4gS4d42 Maria Morganti, Christian Tidona, Masato Hata, Benjamin August 👉 Find all news from PROGEN, EMBL, Bayer, Heidelberg Pharma AG and much more in our newslounge at bioRN website: https://bit.ly/3Yd5fPR

New Liquid Biopsy Method Enables Real-Time Monitoring of Metastatic Prostate Cancer Researchers have developed a novel liquid biopsy methodology that enables the monitoring of disease evolution in patients with metastatic prostate cancer. The study, published in Cancer Cell, leverages the RNA contained in extracellular vesicles shed by tumor cells into the bloodstream to capture the cancer’s genomic and transcriptomic evolution, offering a promising new tool for personalized cancer treatment. The study demonstrates how this liquid biopsy-based approach can detect tumor gene expression through RNA in circulating extracellular vesicles. According to the researchers, these findings could predict treatment response, identify mechanisms of drug resistance, and provide new avenues for studying cancer through non-invasive methods. Extracellular vesicles, which naturally facilitate intercellular communication, carry proteins, lipids, metabolites, RNA, and DNA. These vesicles, when produced by tumor cells, play a crucial role in cancer progression and metastasis. However, their potential as a source of clinically relevant DNA and RNA biomarkers has been largely unexplored until now. The researchers analyzed liquid biopsies from a cohort of 53 patients with metastatic castration-resistant prostate cancer, who had received hormone therapy or chemotherapy. They found that the extracellular vesicles contained tumor-derived genetic material, allowing for the identification of specific mutations and the forecasting of disease evolution. This technique enables the monitoring of on-therapy changes in tumors by analyzing mRNA expression in extracellular vesicles, which is protected from rapid degradation, thus providing clinically relevant information. The study highlights the transcriptomic profile of tumors that could serve as biomarkers of response or resistance to therapy. These findings could significantly expand the opportunities for studying cancer through minimally invasive liquid biopsies. Drug resistance remains a major challenge in more effectively treating cancer. Adaptive mechanisms of resistance occur more rapidly and dynamically than mutations driving acquired resistance. Monitoring these changes as they occur by liquid biopsy will enable real‐time clinical decision‐making and the selection of adaptive treatments to help combat evolving tumor dynamics earlier. #opportunities #strategy #programming #design #team #research #data #health #development #collaboration #projects #testing #immunotherapy #cancer #technology #biotechnology #healthcare #medicine #oncology #precisionmedicine #liquidbiopsy #rna #dna #venturecapital #startup #immunooncology #tcells #innovation #growth #tech #lifesciences #biopharma #oncodxrx #genomics #NGS #CRISPR #gene #geneexpression #artificialintelligence #machinelearning #sequencing

Off-the-Shelf NK Cell Therapies Off-the-shelf NK (natural killer) cell therapies are changing the immunotherapy landscape by providing readily available, scalable treatments for cancer and infectious diseases. Unlike autologous therapies, which rely on harvesting a patient’s own cells, off-the-shelf therapies are derived from healthy donors or engineered from induced pluripotent stem cells (iPSCs). This approach eliminates the time-consuming and expensive processes associated with personalized treatments, allowing for rapid and widespread adoption. One of the key innovations in off-the-shelf therapies is the development of universal donor NK cells. These cells are genetically engineered to reduce immunogenicity, minimize the risk of rejection by a patient’s immune system, and enable universal compatibility. Additionally, iPSC-derived NK cells provide a renewable and stable source of NK cells. By reprogramming iPSCs into NK cells, researchers can produce large quantities of standardized, high-quality cells that can be cryopreserved for long-term storage and immediate use. Off-the-shelf NK cell therapies offer several advantages over autologous therapies. They are more cost-effective due to standardized manufacturing processes and can be manufactured at scale to treat multiple patients from a single batch. Their immediate availability makes them ideal for urgent treatment needs, especially in malignant cancers where time is of the essence. These therapies are also easier to implement in clinical settings, overcoming the logistical challenges associated with personalized cell therapies. Off-the-shelf NK cells are often engineered with chimeric antigen receptors (CAR-NK) to enhance their specificity and efficacy against tumor targets. Other modifications, such as cytokine overexpression (e.g., IL-15), further improve their persistence and function in the tumor microenvironment. Early clinical trials have demonstrated promising results in the treatment of hematological malignancies and solid tumors, demonstrating their safety, scalability, and efficacy. It can be said that off-the-shelf NK cell therapies have paved the way for accessible and transformative immunotherapies, bringing new hope to patients worldwide. Reference [1] Melissa Berrien-Elliott et al., Blood 2023 (https://lnkd.in/g8KxBvKk) #Immunotherapy #NKCells #OffTheShelfTherapies #CAR_NK #CancerResearch #ImmuneOncology #iPSCCells #BiomedicalInnovation #PrecisionMedicine #CancerImmunology #OncologyBreakthroughs #GeneEditing #TumorMicroenvironment #ClinicalTrials

NK Cell Therapies

Off-the-Shelf NK Cell Therapies Off-the-shelf NK (natural killer) cell therapies are changing the immunotherapy landscape by providing readily available, scalable treatments for cancer and infectious diseases. Unlike autologous therapies, which rely on harvesting a patient’s own cells, off-the-shelf therapies are derived from healthy donors or engineered from induced pluripotent stem cells (iPSCs). This approach eliminates the time-consuming and expensive processes associated with personalized treatments, allowing for rapid and widespread adoption. One of the key innovations in off-the-shelf therapies is the development of universal donor NK cells. These cells are genetically engineered to reduce immunogenicity, minimize the risk of rejection by a patient’s immune system, and enable universal compatibility. Additionally, iPSC-derived NK cells provide a renewable and stable source of NK cells. By reprogramming iPSCs into NK cells, researchers can produce large quantities of standardized, high-quality cells that can be cryopreserved for long-term storage and immediate use. Off-the-shelf NK cell therapies offer several advantages over autologous therapies. They are more cost-effective due to standardized manufacturing processes and can be manufactured at scale to treat multiple patients from a single batch. Their immediate availability makes them ideal for urgent treatment needs, especially in malignant cancers where time is of the essence. These therapies are also easier to implement in clinical settings, overcoming the logistical challenges associated with personalized cell therapies. Off-the-shelf NK cells are often engineered with chimeric antigen receptors (CAR-NK) to enhance their specificity and efficacy against tumor targets. Other modifications, such as cytokine overexpression (e.g., IL-15), further improve their persistence and function in the tumor microenvironment. Early clinical trials have demonstrated promising results in the treatment of hematological malignancies and solid tumors, demonstrating their safety, scalability, and efficacy. It can be said that off-the-shelf NK cell therapies have paved the way for accessible and transformative immunotherapies, bringing new hope to patients worldwide. Reference [1] Melissa Berrien-Elliott et al., Blood 2023 (https://lnkd.in/g8KxBvKk) #Immunotherapy #NKCells #OffTheShelfTherapies #CAR_NK #CancerResearch #ImmuneOncology #iPSCCells #BiomedicalInnovation #PrecisionMedicine #CancerImmunology #OncologyBreakthroughs #GeneEditing #TumorMicroenvironment #ClinicalTrials