Abstract Presentation Number: 5444，Section 15 Board2, April 29, 2025, 2:00 PM - 5:00 PM (CST)
ImmuMab® mice enable efficient development of antibody therapeutics by unparalleled diversity across multiple formats
Presenter/Authors
Abstract
This study highlights the latest advancements of ImmuMab® gene-edited mouse platform, engineered with human immunoglobulin germlines to facilitate efficient antibody therapeutic development across diverse formats, including canonical, heavy-chain-only (HCO), common-light-chain (CLC), or combinations thereof. Utilizing massive-fragment across species in situ replacement technology, these mice underwent Mb-scale humanization of immunoglobulin gene fragments in single-step operations, circumventing the cumulative cellular damage associated with traditional transgenic approaches.
These new mice all deliver distinguished immune kinetic profiles featuring rapid initial immune responses and compelling titer plateaus. Since their introductions, the ImmuMab® mouse suite (HK, HKL, HL, HCO, CLC) has consistently delivered highly diversified repertoires across 35+ antibody discovery programs, with no failures due to suboptimal immune responses.
Designed for canonical antibody generation, the ImmuMab HK, HKL and HL mice (the latter two newly introduced), feature up to over 3.2 Mb human Immunoglobulin variable region genes. The ImmuMab HK mice in different project had deliver stable median titers ranging from 72.9k to 656.1k by the third dose, with some maximum titers approaching 1968.3k. Their immune responses exhibit robust resilience against challenging targets, including seven-transmembrane receptors and antigens with over 99% human-mouse homology. Notably, in one hybridoma screening against hROR1, the primary clone positivity rate (OD450 > 0.5) exceeded 33%. Selected monoclonal antibodies demonstrating affinities ranging from 0.001 to 1 nM (by BLI) and internalization rates of 20%-90% (Temperature-dependent). Some antibodies further demonstrated superior cytotoxic efficacy (MMAE-conjugated) compared to benchmark antibody-drug conjugates (ADC).
Additionally, one discovery program with ImmuMab Light® (CLC) mice by rapid immunization (1-week intervals) yielded seven candidate antibodies with picomolar EC50 values (EC50 < 5 × 10-10 M, ELISA) within a single screening cycle. Furthermore, the ImmuMab Heavy® (HCO) mouse enabled rapid heavy-chain-only immune response, reaching titers of 218.7k~656.1k within four weeks and identifying heavy-chain-only antibodies with low single-digit nanomolar EC50 values for both human and cynomolgus monkey antigens.
The ImmuMab® mouse platform enables efficient development of antibody therapeutics across multiple formats. Its robust immune responses and high repertoire diversity make it a powerful tool for generating high-quality candidates, even against challenging targets.
关于超大片段跨物种原位替换技术 (Massive-fragment Across Species In situ Replacement Technology, MASIRT®)
伊米诺康原创核心技术：单次 Mb 级超大片段跨物种原位替换技术。可快速实现包括全人源抗体小鼠，羊驼纳米抗体小鼠，全人源抗体兔等多物种抗体发现平台的搭建。
关于伊米诺康
伊米诺康（Immunocan） 创建于 2020 年，是中国唯一一家专注于下一代创新抗体药物发现平台的生物技术公司，通过基因编辑技术对多种动物进行免疫球蛋白可变区基因替换，获得可生成全人源抗体和多物种纳米抗体的基因编辑动物。伊米诺康致力于为全球药物研发伙伴提供领先的抗体发现平台，共同为疾病治疗带来更安全有效的创新药物。
更多信息，请访问：https://immunocan.com/