Biocytogen provides scientific animal models and systematic bioassays for the preclinical study of antitumor bsAb, including target validation, safety profiles, efficacy evaluation, etc.
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Bispecific antibodies (bsAbs) , designed and manufactured through genetic recombination, chemical conjugation, or quadromas to contain two target-binding units in one antibody-based molecule, could target two independent epitopes or antigens. Upon sequential or simultaneous binding, bsAb acts as a biophysical bridge between two antigens with multiple modes of action (MoA) in vivo to achieve specific effects, including T cell and NK cell engagement, tumor targeting, and immune modulation. BsAbs, particularly T-cell engagers, also promising therapeutic potential in autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, by targeting specific immune cells like B cells and inflammatory mediators.
Nowadays, many bsAbs are being tested in clinical trials for treating a variety of diseases, mostly cancer. Here, we provide scientific animal models and systematic bioassays for the preclinical study of antitumor bsAb, including target validation, safety profiles, efficacy evaluation, etc.
Biocytogen have established a state-of-the-art pharmacology platform for supporting the application of investigational antibodies. For the preclinical study of bispecific antibodies, we have developed different animal models for fitting customized requirements, including syngeneic models, xenograft models, target-humanized models like B-hCD3E and B-hCD3EDG mice, and human immune system reconstitution models. As for in vitro study, our flow cytometry platform and cell base platform support a series of in vitro studies in a quick, reliable, and reproducible way to evaluate the function and MOA of bispecific antibodies, including target validation, intracellular signal transduction, antibody Fc effects (ADCC, ADCP, CDC) and safety evaluation, etc.
(A) Anti-tumor activity of Blinatumomab in B-hCD3E mice.
B-hCD19 MC38 cells were subcutaneously implanted into B-hCD3E mice. Mice were grouped when the tumor size was approximately 50-100mm3
(B) Anti-tumor activity of antibody GR1803 in B-hCD3EDG mice.
B-hBCMA MC38 cells were subcutaneously implanted into B-hCD3EDG mice (female, 6~8 week-old). Mice were grouped when the tumor size was approximately 50~100mm3.
Li, L., Chen, X., Li, Y., & Lou, L. (2022). Pharmacological characterization of gr1803, a novel bcma × cd3 bispecific antibody for multiple myeloma treatment.
Efficacy evaluation of bispecific antibody on human immune system reconstitution models. (A) Human immune system reconstitution models for CD3-based bispecific antibody study. NUGC4 cells (5E6) were subcutaneously implanted after human PBMCs (5E6) were intravenously implanted into B-NDG mice. Anti-human CD3×Claudin18.2 bispecific antibody (AMG 910 analog) inhibited significantly NUGC4 tumor growth in human PBMC reconstituted B-NDG mice
B-NDG mice reconstituted with PBMCs were used for CD3×HER2 bispecific antibody efficacy studies. NCI-N87 cells (1E7) were subcutaneously implanted 3 days before human PBMCs (5E6) were intravenous implanted into B-NDG mice. The animals were grouped into control and treatment when the tumor size was approximately 100-150 mm3 and the percentage of human blood hCD45% were above 10%, at which time they were treated with drugs. (A) Anti human CD3×HER2 bispecific antibody inhibited NCI-N87 tumor growth in human PBMC reconstituted B-NDG mice.
A: Blinatumomab significantly promoted the proliferation of T cells co-cultured with Daudi cells in a dose-dependent manner. B: Blinatumomab showed significantly cytotoxic efficacy in a dose-dependent manner at a 10:1 ratio of Daudi to T cells. C-D: Blinatumomab increased significantly the secretion of IFN-γ and IL-2 in a dose-dependent manner.
Antitumor activity of anti-human CD16A-based Ab in B-hCD16A mice. (A) Anti-human CD16A-based Ab inhibited MC38 tumor growth in B-hCD16A mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCD16A mice (female,13 week-old, n=7). Mice were grouped when tumor volume reached approximately 70 mm3, at which time they were treated with anti-human CD16A-based Ab with doses and schedules indicated in panel B. (B) Body weight changes during treatment. As shown in panel A, anti-human CD16A-based Ab was efficacious in controlling tumor growth in B-hCD16A mice, demonstrating that the B-hCD16A mice provide a powerful preclinical model for in vivo evaluation of anti-human CD16A-based Ab. Values are expressed as mean ± SEM.
Antitumor activity of anti-PD-1/VEGFA bispecific antibody (ivonescimab analog, in-house) in B-hPD-1/hPD-L1/hVEGFA mice. (A) Anti-PD-1/VEGFA bispecific antibody inhibited B-hVEGFA MC38 tumor growth in B-hPD-1/hPD-L1/hVEGFA mice. Murine colon cancer B-hVEGFA MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/hVEGFA mice (female, 8-week-old, n=6). Mice were grouped when tumor volume reached approximately 70-90 mm3, at which time they were intraperitoneally injected with anti-PD-1/VEGFA bispecific antibody indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-PD-1/VEGFA bispecific antibody was efficacious in controlling tumor growth in B-hPD-1/hPD-L1/hVEGFA mice, demonstrating that the B-hPD-1/hPD-L1/hVEGFA mice provide a powerful preclinical model for in vivo evaluation of anti-PD-1/VEGFA bispecific antibodies. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.
The overage of this tumor model is 50%.
| Category Name | Product Name | Product No. | Background | Action |
| T cell engager | B-h4-1BB mice | 110004 | C57BL/6 | |
| B-hCD27 mice | 110006 | C57BL/6 | ||
| B-hCTLA4 mice | 110011 | C57BL/6 | ||
| B-hOX40 mice | 110014 | C57BL/6 | ||
| B-hTIM3 mice | 110018 | C57BL/6 | ||
| B-hICOSL mice | 110037 | C57BL/6 | ||
| B-hCD3EDG mice | 110039 | C57BL/6 | ||
| B-hVSIR mice | 110049 | C57BL/6N | ||
| B-hIL13 mice | 110058 | C57BL/6 | ||
| B-hIL10 mice | 110060 | C57BL/6 | ||
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| Category Name | Product Name | Product No. | Background | Action |
| NK cell engager | B-hPD-1 mice | 110003 | C57BL/6 | |
| B-h4-1BB mice | 110004 | C57BL/6 | ||
| B-hCD27 mice | 110006 | C57BL/6 | ||
| B-hTIGIT mice | 110017 | C57BL/6 | ||
| B-hTIM3 mice | 110018 | C57BL/6 | ||
| B-hPD-1 mice plus | 110019 | C57BL/6N | ||
| B-dPD-1 mice | 110022 | C57BL/6 | ||
| B-hLAG3 mice plus | 110025 | C57BL/6 | ||
| B-hNKG2A mice | 110041 | C57BL/6N | ||
| B-hIL2RA mice | 110066 | C57BL/6 | ||
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| Category Name | Product Name | Product No. | Background | Action |
| Checkpoint-based BsAb | B-hPD-1 mice | 110003 | C57BL/6 | |
| B-h4-1BB mice | 110004 | C57BL/6 | ||
| B-hBTLA mice | 110005 | C57BL/6 | ||
| B-hCD27 mice | 110006 | C57BL/6 | ||
| B-hCD28 mice | 110007 | C57BL/6N | ||
| B-hCD3E mice | 110008 | C57BL/6 | ||
| B-hCD40 mice | 110009 | C57BL/6 | ||
| B-hCD47 mice | 110010 | C57BL/6 | ||
| B-hCTLA4 mice | 110011 | C57BL/6 | ||
| B-hGITR mice | 110012 | C57BL/6 | ||
| MORE >> | ||||
