In Vivo Efficacy

Biocytogen provides high quality in vivo pharmacology services that test efficacy. Our in vivo services use 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 in vivo services 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

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

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.

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

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.