Increasing Possibility of Success by Expanded Antibody Repertoires with Lambda Light Chain - Immunocan Launches New Mouse Strain of Fully Human Antibody Platform: ImmuMab® HKL Mouse

BOSTON, July 17, 2024 /PRNewswire/ -- Immunocan announced the successful construction of new strain of fully human antibody platform: ImmuMab® HKL mouse. This new mouse was created by in-situ replacing the variable region of Immunoglobulin genes of mouse by its counterparts from human. With Lambda light chain genes humanized, ImmuMab® HKL mouse now contains approximately 3.2 Mb of human immunoglobulin variable region genes, making it the humanized mouse with the longest human immunoglobulin variable regions in the world.

Since the first mouse-derived monoclonal antibody drug OKT3 (muromonab-CD3) was marketed in 1986, over 120 antibody drugs from different sources have been approved by FDA and brought clinical benefits to patients. Despite flexibility and well-established application process, ritual use of mice during antibody generation brought limitations for drug development space. Due to the low utilization of Immunoglobulin Lambda genes in wildtype mice (about 5%, varying by strain), antibodies with Lambda light chain (λ-antibodies) have always been under-scrutinized. As of December 31, 2023, only 14 FDA-approved antibody drugs contain Lambda light chain, and most of these are from transgenic mice or human antibody library used in display technologies.

In humans, naturally occurring λ-antibodies are approximately 35% of the antibody repertoire and plays important role in adaptive immunity. Different individuals generate immune repertoires with different preferences of light chain type in response to different immunogens. Within the immune repertoire against the same antigen, λ-antibodies can target different epitopes from κ-antibodies. Therefore, using an antibody generation model containing human Lambda light chains can significantly enhance the epitope coverage of the immune repertoire and increase the success rate of obtaining candidate antibodies fitting target product profile.

By proprietary Massive-fragment Across Species In-situ Replacement Technology (MASIRT®), Immunocan achieved humanization of Lambda light chain variable regions of ImmuMab® mouse, which increased the total humanized immunoglobulin variable region to 3.2 Mb. This innovation provides the industry with source of λ-antibody repertoires of higher diversity and developability compared to existing platforms.

For most antigens, especially in the early stage of discovery programs, the light chain preference of preferred lead antibodies is unpredictable. Using mouse generating a significant quantity of human λ-antibodies can prevent the early exclusion of superior lead molecules during antibody generation, increasing the probability of drug development success.

In addition to ImmuMab® HKL mouse, Immunocan has already constructed platforms including ImmuMab® HK mouse generating fully human antibody (κ-antibodies), ImmuMab Heavy® mouse generating fully human heavy-chain-only antibody (HCAb), ImmuAlpaca® mouse generating alpaca-derived 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.

Immunocan's multi-species antibody generation strategy not only expands the potential for antibody discovery and development but also provides more therapeutic options for treating complex diseases. Immunocan is looking forward to introducing its innovative antibody discovery platforms to global research partners and seek 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.

For more information, please visit: https://immunocan.com/ 

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