RESOURCES

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

June 18, 2025

Development of Preclinical Models for the Evaluation of Conventional and in vivo CAR-T Therapies

Traditional CAR-T therapies require expensive, complex ex vivo T-cell engineering. While in vivo CAR-T generation using lentiviral vectors offers a faster, cheaper alternative, preclinical testing is limited by graft-versus-host disease (GVHD) in immunodeficient mouse models. To overcome this, GemPharmatech developed the NCG-MHC-dKO mouse, featuring dual MHC I/II knockout to minimize GVHD while maintaining human immune cell engraftment. Testing an anti-CD19 CAR lentiviral vector in this model demonstrated successful in vivo CAR-T generation and potent tumor suppression, with no significant GVHD. The NCG-MHC-dKO model enables reliable, long-term evaluation of in vivo CAR-T therapies, enhancing translational research.
June 18, 2025

NCG-X: A Novel Mouse Model For Preclinical Studies Evaluating Humanized Erythroid Reconstitution

Hematopoietic stem cell (HSC) transplantation is critical for treating blood cancers and autoimmune diseases, but existing animal models rely on toxic preconditioning (irradiation/chemotherapy), leading to off-target effects that undermine research validity. To overcome this, we developed the NCG-X mouse by introducing a C-KIT (Val831Met) mutation into the NCG mouse. This model enables human HSC engraftment without irradiation or chemoablation, offering a promising platform for immune and erythroid reconstitution studies.
June 16, 2025

Applications for SLE patient-derived PBMC-induced mouse model in preclinical pharmacological studies

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of auto-antibodies against nuclear antigens, as well as the deposition of immune complexes, and chronic inflammation of target organs such as the skin, joints, and kidneys. Animal models continue to play a crucial role in understanding disease mechanisms and evaluating novel treatment methods. GemPharmatech has developed a humanized SLE mouse model by transferring PBMCs from SLE patients into immunodeficient mice (NCG mice). This resulted in high levels of human auto-antibodies and renal immune complex deposition. Furthermore, this model responded to B-cell directed therapeutic antibodies, which demonstrates its value and potential in evaluating novel therapeutic modalities.
May 18, 2025

Repurposing Oncology Drugs to Treat Autoimmune Diseases

Developing new drugs requires a significant investment of time and economic costs. Drug repurposing therefore has significant advantages over developing new drugs. Humanized SLE models exhibit similar pathological features to those seen in patients with SLE, such as high levels of auto-antibodies and pathogenic B cells, and respond positively to treatment with potentially repurposed oncology therapeutics. As such, these models are valuable for the evaluation of other future repurposed B cell-directed oncology drugs.
May 01, 2025

AACR 2025 Poster Resources

Our nine AACR 2025 posters are now available for download!
December 20, 2024

Mouse Models of anti-PD-1 Resistance Reveals Insights into Resistance Mechanisms

The immune checkpoint molecule PD-1 and its ligand PD-L1 play a pivotal role in tumor immune evasion and progression by thwarting apoptosis induced by the immune system. Despite the significant efficacy of anti-PD-1/PD-L1 therapy against solid tumors, durable responses are observed in only a minority of patients. Many patients fail to experience the full benefits of therapy, with a notable proportion eventually developing acquired resistance. Therefore, establishing robust preclinical models of PD-1 resistance is crucial for unraveling resistance mechanisms and devising novel treatment strategies. Common mechanisms contributing to anti-PD-1/anti-PD-L1 resistance include the absence of suitable tumor antigens, tumor surface MHC molecules inactivation, dysregulated IFN-γ signaling pathways, and the immunosuppressive tumor microenvironment.
December 08, 2024

Spontaneous Systemic Lupus Erythematosus Mouse Model Based on TLR7Y264H Genetic Mutation

Toll-like receptor 7(TLR7) variant Y264H has recently been identified to cause Systemic Lupus Erythematosus (SLE) in human patients. Mice harboring TLR7Y264H mutation in the C57BL/6NCrL background developed spontaneous SLE-like symptoms and organ damage. In order to create clinically relevant mouse models of SLE to evaluate novel therapeutics (especially targeting TLR7), we developed TLR7Y264H mutant mice in both the BALB/c and C57BL/6J background.
November 30, 2024

Chromosome 1 substitution strains, a new resource for pre-clinical MASLD mouse model development

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease and is the leading cause of liver-related morbidity and mortality. However, neither the diet induction model nor the monogenic model based on the laboratory mice could fully imitate human MASH due to the genetic background of existing inbred mice have limitations, such as the lack of genetic diversity and reduced disease susceptibility. Comparing with the laboratory mice, wild mice harbor more genetic polymorphisms to adapt to the natural environment, therefore, introducing the genetic material from wild mice into inbred mice would provide new experiments resources for the complex trait researches. Therefore, GemPharmatech has launched “Wild Mouse” project to develop a complete set of consomics covering all 19 autosomes of mouse, and each chromosome replacement panel will be represented by a population of chromosome substitution strains using captured wild mice across China as chromosome donors. Given that chromosome 1 (Chr1) includes multiple gene loci related to lipid metabolism, we first screened Chr1 substitution strains to search for more appropriate mice model for MASLD research.
November 30, 2024

A persistent hypertension model developed on the AGT humanized mice

As a condition of metabolic syndrome, the prevalence of hypertension increased rapidly in the past three decades and consistent hypertension causes various complications,which impair life quality and even be life-threatening. Angiotensinogen, also known as AGT, is the sole precursor of angiotensin peptides in the RAAS pathway, which is the most carefully studied mechanism of blood pressure and volume regulation. RNAi therapies targeting AGT is a promising approach to treat hypertension and related organ damages. Given that the action of RNA interference drugs based on the complementary base pairing, mouse models for preclinical evaluation on AGT target are limited. In this study, we initially generated AGT humanized mice by introducing the entire AGT gene into the Rosa26 site. Despite the presence of a large amount of human AGT in hAGT mice,the inability of rodent RENIN to convert human AGT to AngI prevents the spontaneous development of hypertension. Therefore, we developed a modified human RENIN virus as a flexible tool to induce the persistence hypertension on our novel AGT humanized mice.

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