In Vivo Efficacy

Biocytogen provides high quality in vivo efficacy studies using genetically modified mice expressing knocked-in human targets in their respective mouse counterpart loci, severely immunodeficient (B-NDG) mice and their variants, as well as wild type mouse strains to support drug discovery and development in oncology, immuno-oncology, autoimmune diseases, and other immune-mediated inflammatory diseases. We have solid experience in testing therapeutics in various forms and combinations, including biologics (monoclonal antibodies and bispecific antibodies), small molecules, and CAR-T therapy. Examples of these studies are provided in the following.

Humanized Immune-checkpoint syngeneic mouse models 

Humanized CD3e-based bispecific antibody efficacy model

Human immune system engrafted mouse model       PDX Models

CAR-T efficacy evaluation models                  CDX Models

 

Please continue reading to view our efficacy studies highlighting biologics and small molecule therapeutics.

Check-point Antibody Efficacy Study in Immune-competent Syngeneic Mouse Models

Check-point-Antibody-Efficacy

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1 mice, where the extracellular domain of human PD-1 replaces that of mouse PD-1 via genomic knock-in. Mice were grouped when the tumor size reached 150 ± 50 mm3 (n=10). The human PD-1 antibody pembrolizumab significantly inhibited tumor growth, confirming that the B-hPD-1 mouse model is a powerful tool for in vivo anti-human PD-1 efficacy studies. Tumor volume: mean ± SEM (A).  Body weight: mean ± SEM (B).

Bispecific Antibody Efficacy Study

Bispecific-Antibody-Efficacy-Study

Murine colon cancer cells MC38 engineered to express human CD19, MC38-hCD19, were subcutaneously implanted into B-hCD3e mice, where the extracellular domain of human CD3e replaces that of mouse CD3e via genomic knock-in. Mice were grouped (n=6) when the tumor sizes were approximately 150 ± 50 mm3. Blinatumomab, a bispecific antibody targeting human CD3e and human CD19, significantly inhibited tumor growth, demonstrating that the B-hCD3e mice are a powerful model for in vivo efficacy evaluation of anti-hCD3e-based bispecific antibodies. Tumor volume: mean ± SEM (A). Body weight: mean ± SEM (B).

Small Molecule Efficacy Study

Small molecules are an important anti-cancer therapeutic modality, either as single agents or in combination with antibody therapeutics. Biocytogen has rich experience in testing small molecule therapeutics, as illustrated in the following example.

Small-Molecule-Efficacy-Study

Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1 mice. Mice were grouped when the tumor size reached approximately 150 ± 50 mm3 (n=8). Combination of anti-hPD-1 antibody pembrolizumab and the chemotherapy drug cisplatin showed additional inhibitory effects on tumor growth than individual agents alone in B-hPD-1 mice. Tumor volume: mean ± SEM (A). Body weight: mean ± SEM (B).

CAR-T Cell Efficacy Study in Highly Immune-deficient B-NDG Mice

CAR-T-Cell-Efficacy

Efficacy of various CAR-T therapy targeting human CD20 was evaluated in highly immune-deficient B-NDG mice inoculated with modified human B cell lymphoma cells, B-Raji-Luc-GFP.  Various CAR-T cells were injected i.v. at the same time of B-Raji-Luc-GFP cells. (A) Luciferase signals as an indicator of tumor load in mice treated with different CAR-T cells. (B) Body weight of treated mice. All values are expressed as mean ± SEM.

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