Cyagen’s HLA transgenic models support thymic education of human T cells, enabling antigen-specific responses critical for immunotherapy research. While TCR diversity data isn’t shown here, these models are validated for functional T-cell development.

Cyagen’s NKG models maintain stable immunodeficiency across generations. Studies show 90% human hepatocyte engraftment with serum albumin levels exceeding 1 mg/mL by 8–12 weeks post-transplant, enabling serial transplantation and 500 million-fold expansion.

The establishment of human tumor xenografts follows a standardized preclinical workflow designed to maintain the biological integrity of the human tumor in an in vivo environment:

Selection of Host Model: Depending on the tumor’s aggressiveness and the study's requirements, an appropriate immunodeficient strain is selected. Options range from BALB/c Nude mice (T-cell deficient) to highly immunodeficient models like NKG (T, B, and NK-cell deficient), which are ideal for difficult-to-engraft samples.

Preparation of Inoculum: * CDX (Cell Line-derived): Human cancer cell lines are cultured, harvested, and suspended in a serum-free medium or a basement membrane matrix (e.g., Matrigel) to enhance engraftment.

PDX (Patient-derived): Freshly archived patient tumor fragments are processed and kept in a cold preservation medium before immediate transplantation.

Inoculation/Transplantation: The material is typically injected subcutaneously (into the flank) for easy monitoring, or orthotopically (into the organ of origin) to better simulate the natural tumor microenvironment and metastatic potential.

Monitoring and Validation: Once the "take" is successful, tumor growth is monitored using calipers or non-invasive imaging (e.g., bioluminescence). The model is validated through histopathological analysis (H&E staining) to ensure the xenograft retains the characteristics of the original human tumor.

Immunodeficient mice are essential for human tumor xenograft models (including both CDX and PDX) due to the biological principle of immune rejection:

Preventing Graft Rejection: A standard mouse with a functional immune system would recognize human cancer cells or tissues as "foreign" invaders. Its T-cells, B-cells, and Natural Killer (NK) cells would immediately attack and destroy the human cells, preventing any tumor growth.

Creating a "Permissive" Environment: By using specialized strains like BALB/c Nude, NOD Scid, or NKG, we remove these immune barriers. This creates a permissive environment that allows the human "graft" to survive, develop a blood supply (angiogenesis), and proliferate as a solid tumor.

Enabling Preclinical Accuracy: These models allow researchers to study the behavior of actual human cancer within a living system (in vivo). Without immunodeficient hosts, it would be impossible to evaluate the efficacy of human-specific anti-cancer therapies before they move toward the drug development pipeline.

The difference lies in the functional status of their immune systems:

Immunocompetent Mice: These mice have a full, functional immune system (including T, B, and NK cells). Common strains include C57BL/6 and BALB/c. They are used to study normal immune responses.

Immunodeficient Mice: These mice have specific genetic mutations that "shut down" parts of their immune system. Strains like BALB/c Nude (lacks T cells) or NKG (lacks T, B, and NK cells) allow for the growth of foreign tissues, such as human tumors, without rejection.

Immunocompetent models are ideal for studies where a host immune response is required. Key applications include:

Syngeneic Tumor Models: Infiltrating mouse-derived tumor cell lines into mice of the same genetic background.

Immune Checkpoint Inhibitor Testing: Evaluating therapies like anti-PD-1 or anti-CTLA-4.

Vaccine Development: Testing the efficacy of vaccines in triggering an immune memory.

Autoimmune Diseases: Studying conditions like rheumatoid arthritis or lupus.

The journey began with the discovery of the Athymic Nude mouse in the 1960s, which lacked T-cells. While revolutionary, these mice retained functional B and NK cells, limiting the types of human tissues they could accept.

The improvement continued with the NOD Scid model, which addressed B-cell deficiency but was hindered by "leakiness" (residual immune activity) and a short lifespan. The major breakthrough came with the development of highly immunodeficient models, such as Cyagen’s NKG mouse. By knocking out the Il2rg gene on a NOD Scid background, researchers successfully eliminated T, B, and NK cells, creating the most receptive host for human cell engraftment to date.

Modern improvements focus on three core areas:

Longevity: Unlike older Scid models, the new generation (like NKG) does not suffer from thymic lymphomas, allowing for long-term studies exceeding 12 months.

Stability: Elimination of "leakiness" ensures that the mice do not spontaneously develop functional murine T or B cells as they age.

Support for Humanization: The latest models are engineered to express specific human cytokines (e.g., IL-15, GM-CSF) to better support the survival and differentiation of specialized human immune cell subsets.

An HIS mouse is a highly immunodeficient mouse that has been "reconstituted" with a functional human immune system. This is typically achieved by transplanting:

Human PBMCs: For short-term studies focusing on mature T-cell responses.

Human Hematopoietic Stem Cells (HSCs): For long-term studies where a full range of human immune cells (T, B, NK, myeloid cells) develops within the mouse’s bone marrow.

These models allow researchers to study the interaction between the human immune system and human tumors in an in vivo setting.

Cyagen offers a comprehensive platform ranging from our proprietary NKG host strains to fully validated HSC-Humanized and PBMC-Humanized models. Furthermore, we provide customized gene-editing services to create niche models that express specific human cytokines or MHC molecules, tailored to your specific drug target requirements.

SCID (Severe Combined Immunodeficient) mice carry a mutation in the Prkdc gene, which results in a near-complete deficiency of functional T and B lymphocytes.

Key Applications:
1. Tumor Xenografts (CDX): Widely used as hosts for the transplantation of human tumor cell lines to evaluate preclinical drug efficacy.
2. Humanization: Serving as a platform for reconstituting the human immune system.
3. Immunology Research: Studying the basic functions of the innate immune system (e.g., NK cells) in the absence of adaptive immunity.

No, standard BALB/c mice are immunocompetent, meaning they have a complete and functional immune system, including T-cells, B-cells, and Natural Killer (NK) cells.

However, confusion often arises because the BALB/c Nude mouse—a popular immunodeficient model—is derived from the BALB/c background. Here is the breakdown:

BALB/c (Wild-type): An immunocompetent inbred strain. It is widely used in immunology, inflammation, and vaccine research because it naturally biases toward a Th2 immune response.

BALB/c Nude (Foxn1): An immunodeficient variant. Due to a mutation in the Foxn1 gene, these mice lack a thymus and cannot produce mature T-cells. They are also hairless, which is their most defining physical characteristic.

A nude mouse is a specialized laboratory strain (most commonly the BALB/c Nude) characterized by a genetic mutation in the Foxn1 gene. This mutation results in two distinct phenotypes:

Athymia: The mouse is born without a thymus, meaning it cannot produce mature T-lymphocytes. This makes the mouse severely immunodeficient.

Alopecia: The mutation also affects the hair follicles, leaving the mouse nearly hairless or "nude."

Because they lack an adaptive T-cell response, they will not reject "foreign" tissues, such as human cancer cells or skin grafts, making them a "permissive" host for cross-species studies.