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

December 10, 2025

Next-Generation Mouse Models for T-cell Engager Preclinical Evaluation

T cell engagers (TCEs) act as a bridge that one end binding to CD3 on T cells and the other end binding to a tumor-associated antigen (TAA) on tumour cells. TCEs physically bring cytotoxic T cells directly next to the tumour cells. This forced proximity triggers the T cells to activate, proliferate and destroy the cancer cells. TCEs redirect the immune responses to eliminate the tumour, independent of TAA presentation. The NCG-MHC-dKO mouse is developed by knocking out both murine MHC class I and class II molecules in NCG mice. GvHD in NCG-MHC-dKO mice is attenuated and the survival of huPBMC-NCG-MHC-dKO mice is significantly prolonged. The growth of NCI-H69 human small cell lung cancer and MM.1S human multiple myeloma were significantly delayed by Tarlatamab in huPBMC-NCG mice. These findings indicate that human immune system reconstituted NCG mouse is an ideal model for TCE efficacy evaluation.
November 19, 2025

Development of Fully Human CD98hc Antibodies to Enhance Delivery of Therapeutic Drugs Across the Blood-Brain Barrier

CD98 heavy chain (CD98hc, also known as SLC3A2), is a type II transmembrane glycoprotein that serves as a critical component of heteromeric amino acid (AA) transporters through its interaction with different light-chain partners. CD98hc is highly expressed in the blood-brain barrier (BBB), where it facilitates receptor-mediated transcytosis and has emerged as a promising target for enhancing dug delivery across the BBB.
In this study, we screened a panel of fully human CD98hc antibodies generated from NeoMab™ transgenic mice. Lead candidates demonstrated robust endocytosis and transcytosis activity in vitro without altering CD98hc receptor abundance or amino acid transport function. These findings highlight fully human CD98hc antibodies as promising transcytosis-enabling modules (TEMs) for shuttling therapeutic agents across the BBB.
November 19, 2025

A Novel Patient-Derived Pre-clinical Mouse Model for Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disease characterized by impaired signal transmission at the neuromuscular junction, caused by auto antibodies targeting acetylcholine receptors (AChR) on skeletal muscle. This disrupts muscle contraction and leads to progressive fatigue and weakness.
To better model MG pathogenesis and therapeutic strategies, we established a humanized NCG mouse model of MG by intraperitoneal injection of peripheral blood lymphocytes (PBLs) from MG patients into immunodeficient NCG mice. This novel patient-derived MG model can recapitulate key immunopathological and histological characteristics of MG patients, presenting as a valuable translational tool for studying disease mechanisms and evaluating potential therapeutic interventions for MG.
November 10, 2025

Integrated Platforms for the Preclinical Evaluation of T-Cell Engagers

T-cell engagers (TCEs), bispecific antibodies that simultaneously target the T-cell surface marker CD3 and a tumor-associated antigen (TAA), have emerged as promising cancer therapeutics. However, their complex mechanisms of action necessitate physiologically relevant models to accurately assess efficacy and safety in the preclinical stage. GemPharmatech established a suite of medium- to high-throughput in vitro assays to screen TCE candidates based on target binding, T-cell activation, and tumor cell killing. Lead molecules were further evaluated in in vivo efficacy studies using both xenograft and syngeneic models. For xenograft studies, we employed NCG and NCG-MHC-dKO mice. The NCG-MHC-dKO model, generated by knocking out murine MHC class I and II genes in the immunodeficient NCG background, minimizes graft-versus-host disease (GvHD) following human PBMC engraftment, thus extending the study window. Our integrated in vitro screening systems and in vivo models—including NCG, NCG-MHC-dKO, and CD3-humanized mouse strains—enable rapid, scalable, and translational evaluation of T-cell engager candidates, providing a robust platform to accelerate immuno-oncology drug development.
November 10, 2025

Development of Preclinical Anti-PD-1 Resistant Models to Uncover Mechanisms of Immune Evasion

Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have transformed cancer treatment, yielding durable responses in some patients. However, both primary and acquired resistance remain major obstacles, limiting therapeutic benefit in many patients. Understanding the mechanisms underlying anti-PD-1 resistance and developing effective counterstrategies require robust, translational preclinical models. To this end, GemPharmatech has established three distinct models of anti-PD-1 resistance. These models provide a powerful platform to investigate mechanisms of immune escape and evaluate novel therapeutic strategies. They are thus indispensable for unraveling the molecular and cellular basis of treatment failure and for guiding the development of next-generation immunotherapies.
November 10, 2025

A Novel Humanized Mouse Model for Preclinical Efficacy Evaluation of Anti-CD47/Anti-SIRPα Therapeutics

CD47 enables tumor cells to evade phagocytic clearance by interacting with Signal Regulatory Protein α (SIRPα) expressed on macrophages and dendritic cells. Therapeutics targeting the CD47-SIRPα pathway promote tumor elimination via two primary mechanisms: 1) blockade of the CD47-SIRPα interaction to facilitate macrophage-mediated phagocytosis, and 2) Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These mechanisms collectively enhance antigen presentation and stimulate adaptive anti-tumor immunity, establishing the CD47-SIRPα axis as a high-priority target in immuno-oncology. To support the translational evaluation of CD47-targeted therapies, GemPharmatech generated a double knock-in mouse strain, BALB/c-hCD47/hSIRPα. This mouse provides a clinically relevant, immunocompetent model for evaluating therapies targeting the CD47-SIRPα axis. It enables comprehensive assessment of efficacy, immune modulation, and safety, thereby addressing key translational challenges in the development of next-generation macrophage checkpoint inhibitors.
November 10, 2025

Enhanced Human Immune System Engraftment in a Novel Triple-Engineered NCG-mTSLP-hIL6-mFlt3 KO Mouse Model

Robust humanized mouse models are critical for evaluating human hematopoietic stem cell (HSC) biology, immune system development, and therapeutic efficacy. The NCG strain provides a superior platform for human HSC engraftment due to severe immunodeficiency. To further enhance human immune system reconstitution, we engineered a next generation strain NCG-mTSLP-hIL6-mFlt3 KO. This model offers a powerful platform for human HSC engraftment and development of a functional, multi-lineage human immune system, including lymphoid (T, B), myeloid (DC subsets), and NK cells. Together with enhanced lymphoid organ development, this model is positioned to be a valuable tool for translational immunology and preclinical evaluation of immunotherapies.
November 10, 2025

MHC Knock-in Mouse Models for Preclinical Evaluation of Cancer mRNA Vaccines

mRNA cancer vaccines represent a next-generation immunotherapy platform with the potential to elicit robust, antigen specific immune responses. Upon in vivo delivery, mRNA vaccines are taken up by antigen-presenting cells (APCs), translated into the tumor associated antigen and presented via MHC molecules to activate adaptive immunity. However, standard mouse models with murine MHC molecules are not suitable for evaluating these MHC-restricted immune responses. GemPharmatech has developed a series of MHC knock-in (KI) models across multiple mouse backgrounds including immunocompetent mice B6, BALB/c, CB6F1 and immunodeficient NCG derived mice. These models express human HLA molecules, enabling the accurate evaluation of antigen presentation, immunogenicity, and therapeutic efficacy of mRNA vaccines. Our diverse portfolio of MHC knock-in mouse models provide more versatile and translationally relevant platforms for preclinical testing of mRNA-based cancer vaccines and combination immunotherapies. These models bridge the gap between murine and human immune systems, enhancing predictive power in vaccine development pipelines.
November 10, 2025

NCG-hIL15 and NCG-hIL2 Mice - Excellent Models for Human Immune Reconstitution of NK Cells

Natural Killer (NK) cells play a critical role in antitumor immunity through direct cytotoxic activity and secretion of immunoregulatory cytokines. They are particularly important in Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), a key mechanism often leveraged by therapeutic antibodies. However, the conventional immunodeficient mouse models show limited capacity to support NK cell engraftment, restricting their translational relevance. To overcome this limitation, we developed two humanized cytokine-expressing immunodeficient NCG mouse models: NCG-hIL2 and NCG-hIL15, engineered to express human IL-2 and IL-15, respectively. NCG-hIL2 was well suited for evaluating ADCC antibodies like Trastuzumab, Margetuximab, Rituximab and Blinatumomab. Both NCG-hIL2 and NCG-hIL15 model offer powerful tools for investigating NK cell biology, cytokine-driven development, and immunotherapy evaluation.

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