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Bispecific antibodies (BsAbs) are experiencing unprecedented growth, drawing the attention of major pharmaceutical companies and biotech firms worldwide. Recently, Merck & Co. (MSD) acquired the global rights to CD19/CD3 BsAb CN201 from Tolerogen Bio for $1.3 billion, underscoring the immense value of these innovative therapeutics in the market. BsAb technology, which targets two distinct molecules simultaneously, not only activates the immune system but also effectively eliminates tumor cells. This dual functionality demonstrates promising potential in the treatment of hematologic malignancies and immune-related diseases.
Fig 1. Mechanism of Action of Bispecific Antibodies
The development of bispecific antibodies (BsAbs) requires rigorous preclinical validation, and mouse bispecific antibodies play a pivotal role in this process. These antibodies are instrumental in the early screening and optimization of BsAb structures, ensuring both efficacy and safety of candidate drugs. They also lay a solid foundation for the subsequent development of humanized antibodies. As therapeutic strategies continue to evolve, mouse BsAbs provide new research pathways for enhancing the efficacy of bispecific drugs.
Key Role of Bispecific Antibodies (BsAbs) and Mouse Models
Bispecific antibodies are a unique class of antibodies capable of targeting two distinct molecules or antigens simultaneously. By bridging two targets, BsAbs can precisely direct immune cells to specific sites, such as tumor cells, and either activate or inhibit specific signaling pathways. This dual-targeting approach enhances therapeutic specificity and efficacy. BsAbs are widely used in various fields, including cancer immunotherapy, hematological disorders, and autoimmune disease interventions.
Mouse bispecific antibodies are specifically designed for use in mouse models, simulating their mechanism of action in human systems. They are critical tools in the early stages of drug development, facilitating the selection and optimization of candidate molecules. Due to their short development cycles, low costs, and the absence of immune rejection (common with non-mouse antibodies), mouse BsAbs provide essential support for the development of humanized antibodies, accelerating the launch of innovative therapeutics.
Fig. 2 Various Designs and Structures of Bispecific Antibodies
Advantages and Applications of Mouse Bispecific Antibodies
■Rapid Screening and Optimization:
Mouse BsAbs provide an efficient platform for fast antibody screening, thanks to their short development cycles.
■Cost-Effective and Easy to Use:
Compared to humanized antibodies, mouse BsAbs are more cost-effective, making them ideal for large-scale screening and analysis.
■Elimination of Immune Rejection:
Using mouse-derived antibodies in mouse models avoids immune rejection, ensuring experimental consistency and stability.
■Support for Humanized Antibody Development:
The data generated with mouse BsAbs provide critical insights for the subsequent development and validation of humanized antibodies.
Common Targets and Applications of Bispecific Antibodies
Target Pair | Application | Clinical Progress / Development Direction | Representative Drugs / Research Progress |
---|---|---|---|
PD-1&PD-L1 | Immune checkpoint blockade, enhancing T-cell activity | Widely used for melanoma, NSCLC, and other solid tumors | Keytruda (pembrolizumab), Opdivo (nivolumab) |
PD-1&CD47 | Suppresses immune evasion, boosts macrophage activity | Phase I/II for refractory solid and hematological tumors | Magrolimab (anti-CD47 antibody) in development |
PD-1&CD3E | Redirects T-cells to increase tumor killing | Experimental stage for solid and hematologic tumors | Multiple platforms in development |
PD-L1&CD47 | Enhances macrophage and T-cell synergy to inhibit tumor growth | Preclinical studies targeting solid and resistant tumors | Intended for PD-1/PD-L1-resistant patients |
PD-L1&OX40 | Activates T-cells to enhance immune response | Phase I trials for recurrent tumors | Developing OX40 agonist combination therapies |
PD-L1&CD28 | Activates co-stimulatory signals, boosts T-cell responses | Early clinical development focusing on tumor microenvironment | Research in progress |
CD198 (CCR7)&CD3E | Induces T-cell killing in hematological malignancies | Clinical trials for leukemia | Targeted antibodies in development for T-cell therapies |
CD20&CD3E | Targets B-cell lymphomas, enhancing immune killing | Phase II/III clinical trials, some therapies approved | Mosunetuzumab (bispecific antibody) |
LAG3&PD-L1 | Dual checkpoint blockade for resistant tumors | Effective in melanoma and other resistant cancers | Relatlimab (anti-LAG3) + Opdivo |
LAG3&PD-1 | Enhances T-cell activation for immune-resistant tumors | Phase III clinical trials | Relatlimab with PD-1 inhibitors in combination |
CD276 (B7-H3)&CD3E | Targets multiple solid tumors, enhances T-cell killing | For tumors resistant to PD-1 therapy | Enoblituzumab in clinical development |
GPC3&CD3E | Targets hepatocellular carcinoma, improves immune response | Phase I/II trials for GPC3-positive liver cancer | Developed by AstraZeneca and Zymeworks |
ROR1&CD3E | Targets triple-negative breast cancer, enhances T-cell killing | Developing ADCs for refractory cancers | VLS-101 in Phase I trials |
Nectin4&CD3E | Targets bladder cancer, improves immunotherapy outcomes | ADCs already approved for bladder cancer | Padcev (enfortumab vedotin) |
CTLA-4&PD-L1 | Dual checkpoint blockade to enhance T-cell activity | Various therapies in clinical trials | Ipilimumab (anti-CTLA-4) + Opdivo |
CTLA-4&OX40 | Enhances anti-tumor immunity by activating T-cells | Phase I studies for recurrent tumors | Multiple combination therapies in development |
AntibodySystem Mouse BsAb Products and Services
To support proof-of-concept (POC) research, AntibodySystem has developed a series of mouse bispecific antibodies specifically for in vivo experiments. These products are available through authorized distributors and are accompanied by fast delivery services. In addition, AntibodySystem offers custom target design and bispecific antibody development services to meet diverse research needs.
■Fully Mouse-Derived Designs:
Avoid heterologous reactions, ensuring compatibility and stability in mouse models.
■IgG-Like Structures:
Provide enhanced stability and activity in experiments, ensuring reliable results.
■Low Endotoxin, High Purity:
Meets strict standards for in vivo studies, ideal for preclinical cancer research.
Recommended Mouse Bispecific Antibody (BsAb) Product List
Catalog No. | Product Name |
---|---|
VMJ04001 | InVivoMAb Anti-Mouse CD276/B7-H3 & CD3E Bispecific Antibody |
VMD10801 | InVivoMAb Anti-Mouse CD19 & CD3e Bispecific Antibody (Iv0224) |
VMC90701 | InVivoMAb Anti-Mouse CD20 & CD3e Bispecific Antibody (Iv0225) |
VMD17203 | InVivoMAb Anti-Mouse CTLA4 & PD-L1 Bispecific Antibody (Iv0226) |
VMD17204 | InVivoMAb Anti-Mouse CTLA4 & OX40 Bispecific Antibody (Iv0227) |
VMG76701 | InVivoMAb Anti-Mouse F4/80 & CD3e Bispecific Antibody (Iv0232) |
VME62001 | InVivoMAb Anti-Mouse TRP-1 & CD3e Bispecific Antibody (Iv0236) |
VME62002 | InVivoMAb Anti-Mouse TRP-1 & CD47 Bispecific Antibody (Iv0237) |
VME62003 | InVivoMAb Anti-Mouse TRP-1 & OX40 Bispecific Antibody (Iv0238) |
VME30301 | InVivoMAb Anti-Mouse CD200 & CD47 Bispecific Antibody (Iv0239) |
VMH02204 | InVivoMAb Anti-Mouse PD-1 & PD-L1 Bispecific Antibody (Iv0240) |
VMG17603 | InVivoMAb Anti-Mouse PD-1 & CD47 Bispecific Antibody (Iv0241) |
VMJ70104 | InVivoMAb Anti-Mouse PD-L1 & CD3e Bispecific Antibody (Iv0242) |
VMG17601 | InVivoMAb Anti-Mouse PD-L1 & CD47 Bispecific Antibody (Iv0243) |
VME43201 | InVivoMAb Anti-Mouse PD-L1 & OX40 Bispecific Antibody (Iv0244) |
VMC83401 | InVivoMAb Anti-Mouse PD-L1 & CD28 Bispecific Antibody (Iv0245) |
VMK06901 | InVivoMAb Anti-Mouse VISTA & PD-L1 Bispecific Antibody (Iv0246) |
VMH72401 | InVivoMAb Anti-Mouse TIGIT & PD-L1 Bispecific Antibody (Iv0247) |
VMD72101 | InVivoMAb Anti-Mouse NKG2D & CD3e Bispecific Antibody (Iv0248) |
VMC27701 | InVivoMAb Anti-Fluorescein & mCD3e Bispecific Antibody (Iv0233) |
VMJ70103 | InVivoMAb Anti-Fluorescein & mPD-L1 Bispecific Antibody (Iv0234) |
VMG17602 | InVivoMAb Anti-Fluorescein & mCD47 Bispecific Antibody (Iv0235) |
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