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RESEARCH AREA: Autoimmune Cardiovascular Disease Cell and Gene Therapy Infectious Disease Metabolism Neurology Oncology Other Rare Disease

November 27, 2024

PDX Models with Differential HER2 Expression for preclinical evaluation of HER2-targeted therapy

Overexpression of the human epidermal growth factor receptor 2 (HER2) is increasingly recognized as a common molecular abnormality in gastric and gastroesophageal cancer. Drugs targeting the HER2 protein have shown promise in treating these cancers. Additionally, there is evidence to suggest that DS-8201a, a HER2-targeted antibody-drug conjugate (ADC), may be effective and safe in treating patients with heterogeneous or low HER2 expression. To aid in the design of personalized or precision drug treatment strategies for HER2-targeted therapies in clinical trials, GemPharmatech offers suitable patient-derived xenograft (PDX) gastric cancer models.
November 20, 2024

NCG-XM Humanized Mice - An Improved Model for Human HSC Immune Reconstitution Without Irradiation

Severely immunodeficient mice engrafted with human hematopoietic stem cells (HSCs) are widely used in immuno-oncology studies to evaluate cancer therapies. GemPharmatech has developed the NCG-XM model, which expresses human granulocyte-macrophage colony-stimulating factor 2 (GM-CSF), interleukin-3 (IL-3), and stem cell factor (SCF), along with a W41/W41 inactivation mutation in the Kit gene. The goal of this model is to support multilineage human immune cell differentiation without the need for irradiation. The HSC-NCG-XM model enables better reconstitution of human T cells, B cells, NK cells, and myeloid cells (such as granulocytes, monocytes, neutrophils, macrophages, and dendritic cells) without requiring murine myeloablation prior to HSC engraftment, typically achieved through sublethal radiation or chemoablation. Furthermore, HSC-NCG-XM mice can survive for over 22 weeks post-engraftment, making them ideal for long-term immuno-oncology studies.
November 20, 2024

Development of a Novel Murine Model, NCG-M/hIL15, for Enhanced Post-HSC Transplantation Immunoreconstruction

Advances in immunology and hematopoietic stem cell (HSC) transplantation have led to the development of murine models that faithfully recapitulate human immune responses. GemPharmatech has developed the NCG-M/hIL15 model, which expresses human granulocyte-macrophage colony-stimulating factor 2 (GM-CSF), interleukin-3 (IL-3), stem cell factor (SCF), and interleukin-15 (IL-15) in the severely immunodeficient NCG mouse. The goal of developing this model is to support a broader reconstitution of the human immune system, including T cells, myeloid cells, and NK cells, following HSC engraftment.
November 20, 2024

An Improved PBMC Humanized Xenograft Model for Preclinical Evaluation of Immune Checkpoint Inhibitors

Immuno-oncology (I-O) therapies have been extensively explored in recent years, particularly immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1 (PD-1) and PD-ligand 1 (PD-L1) inhibitors. Robust and stable animal models are essential for advancing preclinical research and addressing challenges such as low response rates to anti-PD-1/PD-L1 therapies and drug resistance.
GemPharmatech has developed a human peripheral blood mononuclear cell (PBMC)-based humanized xenograft model. In this newly established model, human PBMCs are mixed with human tumor cell lines (including A-431 epidermoid carcinoma) and inoculated subcutaneously into the right flank of immunodeficient NCG mice. This PBMCs-cancer cell lines mixed injection model of NCG mice provides a valuable opportunity to evaluate the in vivo efficacy of immune checkpoint inhibitors.
November 20, 2024

BALB/C-hIL12RB1/hIL12RB2 Serves as a Robust Mouse Model to Evaluate Novel Human IL-12 Therapeutics

Interleukin-12 (IL-12) is a multifunctional cytokine predominantly produced by activated inflammatory cells. IL-12 plays a pivotal role in orchestrating the immune response of Th1 cells, promoting interferon (IFN-γ) production, and enhancing the activation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Preclinical investigations have highlighted IL-12's ability to stimulate T cells and NK cells within the tumor microenvironment, leading to potent anti-tumor effects, thereby positioning IL-12 as a promising therapeutic target. GemPharmatech developed a novel mouse model expressing human IL-12RB1 and IL-12RB2 (BALB/c-hIL-12RB1/hIL-12RB2), providing a powerful tool to evaluate novel human IL-12 therapeutics.
November 20, 2024

Phenotypic Validation of Humanized IgA1 and CD89 Transgenic Mice as a Model for IgA Nephropathy-Like Autoimmune Disease

The etiology of IgA nephropathy (IgAN) remains only partly understood, but the presence of IgA antibodies together with the myeloid IgA receptor FcαRI/CD89 complexes in the circulation of patients is considered a specific pathogenic factor for mesangial deposition. The absence of a CD89 ortholog in rodents, coupled with the differences in the IgA systems between humans and mice, further hinders exploration of IgAN pathogenesis. To better understand the pathogenesis of IgAN, we developed a transgenic mouse model expressing human IgA1 and CD89 (B6-Cd14-hCD89/hIGHA1), in which CD89 is expressed under the control of an endogenous murine CD14 promoter on blood and tissue monocytes/macrophages. This results in a relevant preclinical mouse model useful for the evaluation of CD89 and IgA1-targeted therapies. The B6-Cd14-hCD89/hIGHA1 mice exhibited an IgAN-like phenotype. This novel model can contribute significantly to unraveling the mechanisms underlying IgAN and provide a clinically relevant mouse model for evaluating novel therapeutics against IgAN.
November 20, 2024

Humanized BAFF Transgenic Mice Develop Autoimmune Manifestations

B-cell-activating factor (BAFF) plays a critical role in B cell survival, and its elevated expression can contribute to the presence of autoreactive B cells, potentially leading to autoimmune conditions like Systemic Lupus Erythematosus (SLE). To deepen our understanding of these mechanisms, GemPharmatech developed a transgenic mouse model featuring human BAFF overexpression. This model offers insights into SLE pathogenesis and serves as a relevant preclinical tool for assessing therapies targeting B cells.
August 26, 2024

Establishment of Bleomycin-Induced Scleroderma Mouse Model on HSC-NCG-IL15 Humanized Mice

Systemic sclerosis (SSc), also known as scleroderma, is a rare autoimmune connective tissue disorder associated with significant morbidity and mortality. Numerous studies have reported the involvement of the immune system, particularly T, B, and NK cell-mediated responses, in SSc pathogenesis. However, the underlying mechanisms remain elusive. Therefore, the development of a humanized immune system reconstitution mouse model is essential for advancing such investigations. In this study, we utilized Bleomycin (BLM) to induce a scleroderma mouse model in HSC-NCG-IL15 mice.
August 26, 2024

A Novel Humanized Rheumatoid Arthritis Mice Model for Therapeutic Assessment

Rheumatoid Arthritis is caused by a complex immune system disorder. In this study, we developed a RA disease model induced in humanized HSC-NCG-M mice to mimic manifestations seen in patients. This model incorporates human innate and adaptive immune cells, providing valuable insights for studying RA mechanisms and evaluating drug efficacy.

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