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

小鼠杂交瘤的细胞筛选以改进单克隆抗体的发现

• 批准号: 10696698
• 负责人: Rama Devudu Puligedda
• 金额: $ 35万
• 依托单位: OCMS BIO, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10696698
• 关键词: Address; Advanced Development; Affect; Antibodies; Antibody Specificity; Antibody Therapy; Antigens; B-Lymphocytes; Binding; Biological Assay; Biomedical Research; C-reactive protein; Cell Line; Cell fusion; Cell membrane; Cell secretion; Cell surface; Cells; Clinical; Clinical Research; Clonal Expansion; Clone Cells; Cloning; Comparative Study; Complex; Consumption; Development; Diagnostic; Diagnostics Research; Elements; Engineering; Enzyme-Linked Immunosorbent Assay; Generations; Goals; Human; Human Cloning; Human poliovirus; Hybrid Cells; Hybridomas; Image; Immunize; Immunoglobulin G; Immunoglobulin Genes; Individual; Industrialization; Laboratories; Life; Maintenance; Market Research; Marketing; Methods; Modernization; Monoclonal Antibodies; Mus; N-Methyl-D-Aspartate Receptors; Oryctolagus cuniculus; Phase; Preparation; Process; Property; Rapid screening; Reagent; Reproducibility; Research; Resources; SARS-CoV-2 antigen; Specificity; Splenocyte; Surface; System; Therapeutic; Therapeutic Monoclonal Antibodies; Therapeutic Research; Time; Transgenic Mice; antibody diagnostic; cost; cost effective; fluorescence imaging; human monoclonal antibodies; improved; innovation; novel; process improvement; research and development; screening; success; timeline; tool

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.

概括 OCMS Bio，LLC正在寻求改变单克隆抗体（MAB）发现并通过 开发基于创新的细胞方法，开发单克隆抗体（OCMS）筛选平台 大大改善了抗体发现的杂交方法。单克隆抗体已经成为 现代临床治疗学，诊断和生物医学研究的基本要素。杂交瘤 方法是生成mAB的最古老，最健壮的方法之一。绝大多数mabs 临床疗法和诊断方法是通过杂交瘤方法产生的。但是，这种方法并非没有 由于需要串行限制稀释稀释，因此缺点，因为这是极其劳动量和耗时的，所以 克隆传播和ELISA筛选，这基本限制了可以是的mAb的总数 筛选。为了改善此过程，OCMS Bio开发了一种方法，其中mAB从OCMS分泌 杂交瘤连接到细胞表面，通过创新的锚链链系统分泌它们， 可以通过标准成像工作流对表达进行快速筛选和表征。这 消除了对广泛克隆和基于ELISA的筛选的需求，并有望减少努力 与传统的杂交瘤方法相比，需要将mAB筛查超过80％。此外，OCM 方法支持发现具有理想特异性和可发展性参数的稀有mAb，这是 由于克隆和筛选瓶颈而导致传统杂交瘤方法受到严重限制。 OCMS生物已经证明了使用OCMS的杂交瘤形成和人物mAB的表征 在几个人类系统中接近。 OCMS生物还证明了与小鼠成功形成的杂交瘤 脾细胞。这项研究的目的是开发一种使用鼠标使用OCMS方法的方法 脾细胞并严格证明1）杂交瘤形成的可重复的细胞融合，2）稳定表达 OCMS锚和3）OCMS方法大大减少了与之相关的时间和精力 与传统的杂交瘤方法相比，MAB发现。这些目标的成功将有实质性 随着OCMS方法将适合当前MAB开发工作流程，商业和临床影响 减少成本，精力和开发时间表，以开发新颖的基于MAB的新型生命 治疗和诊断。