Platform for the rapid development of new pathogen-directed humanized or fully human monoclonal antibody candidates (MEMUMAB)

Monoclonal antibodies are transforming modern medicine. At Helmholtz Infection Medicine Hannover at MHH, bringing together uniting TWINCORE and CiiM, advanced cutting-edge technologies and AI drive the development of next-generation human antibodies against targeting major infectious diseases.

Project description

Monoclonal antibodies (mAbs) have become central to modern medicine and biomedical research. Over the past decade, their use has expanded rapidly across scientific and therapeutic fields, and their economic impact is expected to continue growing in the years ahead. At Helmholtz Infection Medicine at MHH (HMIM) bringing together TWINCORE and CiiM, we operate the jointly managed MEMUMAB platform dedicated to the development of novel humanized and fully human monoclonal antibodies. This integrated technology hub combines state-of-the-art technologies, including rapid cloning of variable region sequences from mouse hybridomas, as well as direct cloning of immunoglobulin variable regions from single antigen-specific human B cells or humanized mouse models. These discovery pipelines are enhanced by AI-driven antibody optimization and advanced engineering strategies, such as the targeted modification of the Fc domain to tailor effector functions and improve therapeutic performance. Together, these technologies form a dynamic innovation hub for next-generation antibody discovery and design. The platform supports the development of antibodies relevant to infection research such as neutralizing mAbs targeting HBV, RSV, TBEV, rabies and Nipah virus as well as anti-bacterial antibodies and candidates for other high-impact biomedical applications.

Offered technologies

The MEMUMAB platform unites experts from different teams and centres for the seamless generation and development of mAbs under one roof and opens this technology to scientists at MHH, HZI and beyond. Among others, the following technological solutions can be offered:

1. Hybridoma sequencing and mAb humanization
   Immunoglobulin variable region sequences can be sequenced from mouse hybridoma cell lines in a matter of days. Based on the sequence, recombinant mAbs, either as mouse, chimeric or humanised antibodies, are produced under serum-free conditions.
    
2. Cloning of fully human mAbs from B cells
   Antigen-specific B cells isolated from human blood can be detected by bait proteins. After single-cell RNA-seq of the V(D)J regions, sequences are identified and expressed as recombinant mAbs.
    
3. Cloning of fully human mAbs from humanized mouse models
   For some targets such as emerging or lethal viruses, human blood donations may not contain B cells with sufficient frequency or affinity. In such cases, a humanized mouse model is being used to in vivo prime antigen-specific B cells against these target proteins.
    
4. Recombinant mAb production
   Upon synthesis of heavy and light chain expression vectors, Expi-CHO cells are used to express the mAb candidates. The platform offers a standardized and automated workflow for recombinant mAb expression, purification and quality control of the generated mAbs.
    
5. AI-based mAb optimization
   The coming age of AI-based biotechnology helps to characterize the specificity of B cells detected in clinical specimens by in silico approaches, giving rise to a novel era of AI-based immunology. Furthermore, also the de novo generation or affinity maturation of antibodies with AI-based software is possible.
    
6. Optimization of Fc-mediated effector functions
   After binding, antibodies can interact with and activate Fc receptors on innate immune cells. This leads to opsonophagocytosis of infectious particles and/or the lysis of infected cells. In rare instances, Fc-mediated interactions can result in antibody-mediated enhancement of infection. However, Fc-mediated immunity may be indispensable for protecting against infection in other cases. Therefore, libraries of antibody candidates will be constructed, each with the same Fab part, but with one of up to 50 natural or artificial antibody Fc variants to fine-tune (enhance or decrease) specific Fc effector.
    
7. Functional characterization of mAbs
   After purification, mAbs are tested for antigen-specificity (ELISA, virus neutralization assays), their binding affinity (BLI analysis), and their biological Fc-mediated functions.
    
8. Innovative in vivo delivery
   Currently, we are developing RNA- and AAV-based approaches to express mAbs within the body. These approaches have the advantage that liposomal nanoparticle (LNP) formulated RNA as well as AAV are relatively easy to produce according to GMP standards at relatively low cost.
    
9. Industry cooperation and exploitation
   The partner institutions HZI, MHH, TWINCORE and CiiM have exploitation offices that cooperate and support developments with commercialization potential