On-cell screening of mouse hybridomas for improved monoclonal antibody discovery

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SUMMARY OCMS Bio, LLC is seeking to revolutionize monoclonal antibody (mAb) discovery and screening through the development of an on-cell monoclonal antibody (OCMS) screening platform, an innovative cell-based approach to substantially improve the hybridoma method for antibody discovery. Monoclonal antibodies have become essential elements in modern clinical therapeutics, diagnostics, and biomedical research. The hybridoma approach is one of the oldest and most robust methods for generating mAbs. The vast majority of mAbs for clinical therapeutics and diagnostics are generated by hybridoma methods. However, this approach is not without drawbacks, as it is extremely labor intensive and time consuming, because of the need for serial limiting dilutions, clone propagation, and ELISA screening, which substantially limits the total number of mAbs that can be screened. To improve this process, OCMS Bio has developed an approach in which mAbs secreted from OCMS hybridomas are attached to the surface of the cells that secrete them via an innovative anchor-linker system, which enables rapid screening and characterization of expression with standard imaging workflows. This eliminates the need for extensive cloning and ELISA-based screening and is expected to decrease the effort required to screen mAbs by over 80% compared to the traditional hybridoma approach. Furthermore, the OCMS approach supports the discovery of rare mAbs with ideal specificity and developability parameters, which are severely limited in traditional hybridoma approaches due to cloning and screening bottlenecks. OCMS Bio has demonstrated hybridoma formation and the characterization of human mAbs using the OCMS approach in several human systems. OCMS Bio also demonstrated successful hybridoma formation with mouse splenocytes. The goal of this research is to develop a method for using the OCMS approach with mouse splenocytes and rigorously demonstrate 1) reproducible cell fusion for hybridoma formation, 2) stable expression of the OCMS anchor, and 3) that the OCMS approach substantially reduces the time and effort associated with mAb discovery, compared to the traditional hybridoma approach. Success with these goals will have substantial commercial and clinical impact as the OCMS approach will fit within current mAb development workflows and reduce costs, effort, and development timelines for customers to develop novel lifesaving mAb-based therapeutics and diagnostics.