Oncology and Immuno-Oncology INSIGHTS

Targeting Resistance to Immuno-Oncology Therapies in a Humanized Mouse Model

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Despite extensive global research activities and recent breakthroughs in therapeutics targeting the immune system in cancer patients, the clinical response to treatment can be transient or incomplete. This is due to the ability of cancer cells to adapt to environmental stress, including therapeutic insult, which contributes to tumor evolution and drug resistance. Hence a vast majority of tumor diseases remain difficult to treat and substantial, long-lasting treatment...  Read More

Myeloid Cell-Associated Chemokines in Humanized Immune System Mice

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The interaction between chemokines and their receptors on immune cells is required for immune cells to move throughout the body and into peripheral tissues. Where these human chemokines come from and their levels in humanized immune system (HIS) mice has, until recently, been an unanswered question. HIS mice include NOG, NOG-EXL, and NSG-SGM3 mice that have been engrafted with human CD34+ hematopoietic stem cells (HSCs). In a...  Read More

Important Differences in Human Cell Frequencies, Cytokine Profiles, and Survival between Humanized NOG-EXL and NSG-SGM3 Mice

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Humanized immune system mice are valuable tools for a wide variety of research including studies in immuno-oncology, autoimmune, and infectious disease. But understanding the utility of such models has been hampered somewhat by the wide variety of humanization protocols in use as well as donor-specific effects. The Details Matter When It Comes to Humanization The process to generate a humanized immune system mouse is complex. Many different...  Read More

The Role of NK Cells as an Immunotherapeutic

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The field of immuno-oncology continues to grow and its focus now includes various therapeutic approaches modulating one or more human immune cell types. T cells have been the most widely investigated and are the target of a spectrum of biologics; examples include manipulation of native T cells by checkpoint inhibitors and adoptive cell therapies such as CAR-T cells or the ex vivo expansion of TILs. The FDA...  Read More

Webinar Q&A — Case Study: Variance and its Implications on Study Design in the huNOG-EXL

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Schedule Consultation Dr. Janell Richardson recently presented a webinar on a case study that explored variance and its implications on study design in the huNOG-EXL, a humanized immune system (HIS) model. HIS models are the only in vivo model types to date that allow investigators to study, in real time, human immune cell function under both physiological and pathological conditions. Dr. Richardson provided an overview of HIS...  Read More

Myeloid Cells in Humanized Mice and Cancer Immunotherapy

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Immuno-oncology researchers are looking beyond T cells to other immune cells for the next cancer breakthrough. Myeloid cells (cells that originate from the common myeloid progenitor derived from hematopoietic stem cells in the bone marrow) are among those new targets. This class of immune cells includes monocyte and granulocyte lineages including macrophages, dendritic cells, mast cells, basophils, eosinophils, and neutrophils. Myeloid cells have an important role in...  Read More

Considerations for Performing a Successful Syngeneic Tumor Study

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As the focus of cancer treatment has shifted—from directly targeting and destroying a tumor to leveraging the body's immune system to fight the tumor—there has been a corresponding change in how researchers use animal models in their preclinical oncology studies. While xenograft studies utilizing immunodeficient models once served as the primary approach for oncology research, the rise in immunotherapy has moved syngeneic tumor models back into the...  Read More

Antibody-deficient mice overcome obstacles to efficacy testing of biologics

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Learn how the Jh Mouse Supports Syngeneic Studies Immunogenicity can obscure efficacy in early preclinical research Biologic drugs such as monoclonal antibodies or RNA therapies can trigger immune reactions (immunogenicity) upon treatment. Such immune reactions can result in reduced drug efficacy as well as safety issues. This can be a problem not only in the clinic, but also in the discovery phase. Administration of monoclonal antibodies and...  Read More

Putting Humanized Immune System Models to Work in Drug Discovery

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Researchers today have access to sophisticated human immune system (HIS) mouse models that enable them to ask questions that simply weren't possible to explore with more basic models. While HIS models were once considered interesting tools, albeit mostly academic, now they are widely used in pharmaceutical and biotech companies for research on a variety of disease states. Understanding how HIS models have evolved, the various immune cell...  Read More

How Humanized Immune System Models Are Enhancing Biologics Drug Discovery

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Biologics drug discovery is clearly on the rise as evidenced by the growing number of drug approvals in this therapeutic category. During 2018-2019, the US Food & Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) approved 27 new biologic drugs compared to 19 approved in the previous two-year period1. Biologics also make up an increasing percentage of R&D pipelines; per the 2019 Pharmaprojects Pharma R&D...  Read More

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