Mice carrying the full-length human immunoglobulin loci produce antigen-specific human antibodies with the lambda light chain
Kazuto Shimoya,
Takashi Moriwaki,
Kanako Kazuki,
Akane Okada,
Shigenori Baba,
Yuana Masuda,
Satoshi Abe,
Yasuhiro Kazuki
Affiliations
Kazuto Shimoya
Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Takashi Moriwaki
Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Department of Chromosome Biomedical Engineering, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Kanako Kazuki
Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Akane Okada
Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Shigenori Baba
Department of Chromosome Biomedical Engineering, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Yuana Masuda
Department of Chromosome Biomedical Engineering, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Satoshi Abe
Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Corresponding author
Yasuhiro Kazuki
Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Department of Chromosome Biomedical Engineering, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Chromosome Engineering Research Group, The Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan; Corresponding author
Summary: The development of antibody drugs through animal immunization typically requires the humanization of host antibodies to address concerns about immunogenicity in humans. However, employing an animal model capable of producing human antibodies presents the opportunity to develop antibody drugs without the need for humanization. Despite the ratio of human immunoglobulin (Ig) κ to Igλ usage being approximately 60%:40%, the majority of approved antibody therapeutics are kappa antibodies, and the development of lambda antibodies as therapeutic agents has lagged behind. Therefore, in this study, we developed mice carrying the IGH and IGL loci (IGHL), which can produce human lambda antibodies, using mouse artificial chromosome (MAC) vectors. We demonstrated that IGHL mice consistently retain the human lambda antibody locus integrated on the MAC across generations and can be induced to produce specific antibodies upon antigen stimulation. These findings provide a promising platform for advancing lambda antibody drugs, which have historically been neglected.
