Shanghai, China – August 14, 2025 – Immunocan announced a milestone achievement with its ImmuMab Heavy® mouse: high affinity (sub-nanomolar EC50) human Single-domain Antibodies(SdAb) were obtained with no aggregation observed.
Single domain antibodies are highly favored in current antibody engineering due to their flexibility as modular domains of multi-specifics. Conventional single domain antibody discovery relies on natural heavy-chain-only antibody(HCAb) generating animals, (camelid species) as models, but this approach often suffers from low success rates and difficulty in obtaining desirable candidate antibodies. Replacing camelids with mouse models that carry human antibody heavy-chain variable regions has become a key technological trend in SdAb discovery and development. However, these models frequently face challenges such as poor immune response and a tendency for the resulting human SdAb to aggregate, which significantly limits their application. Immunocan has addressed these issues by employing its proprietary massive-fragment across species in situ replacement technology (MASIRT®) to develop the innovative ImmuMab Heavy® mouse. This model overcomes the aggregation problems commonly seen with human-derived SdAbs. This marks another breakthrough for Immunocan’s leading gene-editing technology in the field of antibody discovery model animals.
The ImmuMab Heavy® mouse exhibited robust and rapid immune kinetics upon antigen immunization (Figure 1a).Phage screening following protein panning achieved a high hit rate of up to 60% (OD450 > 5 NC signal), with 24% of clones exhibiting high signal intensity (OD₄₅₀ > 10 NC signal). (Figure 1b). Multiple high-affinity antibody candidates were identified, exhibiting an EC₅₀ < 1 nM (Figure 1c). Antigen-binding clones were identified through hybridoma screening, followed by cell culture, expression, and one-step purification via Protein A affinity chromatography. Under non-reducing PAGE analysis, the antibody was predominantly present as a naturally active dimer, with no significant aggregation detected.(Figure 1d). The lead antibody selected via phage display screening was transiently expressed at yields exceeding 300 mg/L and purified using one-step Protein A chromatography. It was stably stored in PBS at concentrations above 2 mg/mL. PAGE analysis confirmed a purity of up to 100% (Figure 1e), with SEC analysis showing monomer content >95% and no significant high-molecular-weight aggregates (Figure 1f)
Figure 1. Fully Human SdAb Discovery Using ImmuMab Heavy® Mouse
The above progress fully demonstrates Immunocan’s unique capability in developing complex animal models leveraging its Mb scale gene-editing technology, providing a unique advantage in continuously innovating antibody discovery technologies to empower drug development. It also validates Immunocan’s capability to continuously deliver high-value, high-quality, and leading platforms in antibody discovery.
Immunocan has already constructed platforms including ImmuMab HK/HKL/HL® mouse generating fully human antibody (human κ-antibodies or λ-antibodies or both by different strains respectively), ImmuMab Heavy® mouse generating human HCO antibody, ImmuAlpaca® mouse generating alpaca HCO antibody, and ImmuMab Light® mouse generating fully human common-light-chain antibody. ImmuHeavy® Rabbit is currently under construction to generate rabbit heavy-chain-only antibodies. By continuously innovating in-vivo antibody discovery platforms, Immunocan aims to help partners accelerate the development of novel therapeutics.
As the world’s only platform currently leveraging a unique and groundbreaking gene-editing technology, Immunocan’s multi-species, format-agnostic antibody generation strategy broadens the scope of antibody discovery and development by leveraging the immune systems of diverse animal models and enabling compatibility with a wide range of therapeutic antibody formats. As the most upstream platform for antibody generation, it can seamlessly integrate with numerous downstream innovative technologies, unlocking synergies that deliver value beyond the sum of their parts. This versatile approach enhances the likelihood of identifying high-quality candidates and supports the development of innovative treatment options for complex diseases. Immunocan is looking forward to introducing its innovative antibody discovery platforms to global research partners and seeking collaboration to bring safer and more effective therapeutic products to patients worldwide.
About the Massive-fragment Across Species In-situ Replacement Technology (MASIRT®)
Immunocan's core technology features one-step gene replacement at Mb scale between two species. Its advantageous genome-engineering efficiency enables rapid construction of multiple specialized antibody discovery platforms, including mice generating fully human antibodies or alpaca antibodies and rabbits generating fully human antibodies (under construction).
About Immunocan
Immunocan was founded in 2020 and specializes in using gene editing technology to replace immunoglobulin variable region genes in various animals, resulting in genetically engineered animals capable of producing fully human antibodies and other innovative modalities. The company is committed to offering cutting-edge antibody discovery platforms to worldwide drug research partners, with the goal of developing safer and more effective treatments for human diseases.
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