Oncology and Immuno-Oncology INSIGHTS

Revisiting the Humanized NOG-EXL: A Preclinical Model for Cell Therapy Applications

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By definition, cell therapy is the transfer of autologous or allogeneic cellular material into a patient for medical purposes. Although the technique was first explored in the late 19th century, it has only recently gained traction as a standard of care in the medical field. Global market share is estimated to expand from $9.5 billion in 2021 to $23 billion in 20281. With respect to immuno-oncology applications,...  Read More

Humanized Mice as a Model for Reprogramming Tumor-Associated Macrophages

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Cancer immunotherapies enhance the body's own immune system to control and eliminate tumors. Most clinical-stage immunotherapies target T cells of the adaptive immune system, especially cytotoxic CD8+ T cells. Myeloid cells have risen to prominence as worthwhile targets for immunomodulation. Within the immune landscape of the tumor microenvironment (TME), tumor-associated macrophages (TAMs) significantly influence the activities of T cells and the outcome of T cell-targeting therapies. TAMs...  Read More

Regulatory T Cells in Humanized Immune System Mice

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Regulatory T cells (Tregs) are a critical component of the immune system for regulating inflammatory responses. In the context of immune-mediated diseases, such as cancer or graft-versus-host disease (GvHD), Tregs can either drive or suppress disease pathogenesis. This two-sided role for Tregs and their impact on such a broad spectrum of diseases makes them an important focus of study in immuno-oncology and autoimmunity. Preclinical models of these...  Read More

HLA Mice as a Model to Study T Cell Responses Restricted by Human MHC

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Introduction to HLA and MHC An HLA (Human Leukocyte Antigen) or human MHC (Major Histocompatibility Complex) is a group of surface protein complexes that presents antigens to downstream immune cells to activate the adaptive immune system against foreign pathogens or injured cells. These molecules are critical for modulating T cell responses and play a major role in several autoimmune diseases including diabetes, arthritis, and multiple sclerosis. The...  Read More

Webinar Q&A — Applications of Transgenic HLA Mice, From Vaccines to Immuno-oncology

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Dr. Courtney Ferrebee recently presented a webinar titled "Applications of Transgenic HLA Mice, From Vaccines to Immuno-oncology". The webinar presented an overview of Taconic Biosciences' catalog of class I and class II transgenic HLA models, including an introduction to the HLA system and the role it plays in therapeutic applications, as well as the history of how Taconic's models were generated. She then presented various specific case...  Read More

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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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 mice and...  Read More

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