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

摘要 OCMS Bio，LLC正在寻求通过 一种基于细胞的创新方法--细胞内单抗筛选平台的研制 以大幅改进杂交瘤发现抗体的方法。单抗已经变成了 现代临床治疗学、诊断学和生物医学研究的基本要素。杂交瘤 方法是最古老和最健壮的mAb生成方法之一。绝大多数单抗用于 临床治疗和诊断是由杂交瘤方法产生的。然而，这种方法并非没有 缺点，因为它是极其劳动密集型和耗时的，因为需要连续的限制稀释， 克隆繁殖和ELISA筛选，这极大地限制了可以 已经检查过了。为了改进这一过程，OCMS Bio开发了一种从OCMS分泌单抗的方法 杂交瘤通过创新的锚链系统附着在分泌杂交瘤的细胞表面， 这使得能够使用标准成像工作流程快速筛选和表征表达。这 消除了广泛的克隆和基于ELISA的筛查的需要，并有望减少工作量 与传统的杂交瘤方法相比，筛选单抗所需时间提高了80%以上。此外，OCMS 方法支持发现具有理想的特异性和可开发性参数的稀有单抗，这些参数是 由于克隆和筛选瓶颈，传统杂交瘤方法受到严重限制。 OCMS Bio已经证明了杂交瘤的形成和使用OCMS鉴定人类单抗 在几个人类系统中的方法。OCMS Bio还成功地在小鼠身上形成了杂交瘤 脾细胞。本研究的目标是开发一种在小鼠身上使用OCMS的方法 并严格证明了1)可复制的细胞融合可形成杂交瘤，2)稳定表达 3)OCMS方法大大减少了与以下内容相关的时间和工作量 单抗的发现，与传统的杂交瘤方法相比。这些目标的成功将会有很大的 商业和临床影响，因为OCMS方法将适合当前mAb开发工作流程和 降低客户开发基于mAb的新型救生单抗的成本、工作量和开发时间表 治疗和诊断学。

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.