Loss of Antibody Productivity by Hybridomas: Is DNA Loss Responsible?

9809820健康杂交瘤等融合细胞系的不稳定性仍然是生产具有重要商业价值的单抗的主要障碍。在以前的工作中，这些PI证明杂交瘤细胞生产力的降低是由于形成了一个非生产性细胞亚群，而不是整个生产线的减弱。非生产细胞不产生必需的抗体重链(HC)。HC产生的丧失可能是DNA丢失或突变的结果，或者是某种影响mRNA产生、调节或翻译的事件的结果。在这项提案中，将研究DNA丢失假说。***

9809820 Heath The instability of fused cell lines such as hybridoma remains a major complication in the production of commercially important monoclonal antibodies. In previous work, these PIs demonstrated that the diminished productivity of hybridoma cells is due to the formation of a non-productive cell subpopulation rather than a weakening across the line. The non-productive cells were not producing the essential antibody heavy chain (HC). The loss of HC production can be the result of DNA loss or mutation or some kind of event affecting mRNA production, regulation, or translation. In this proposal the DNA-loss hypothesis will be investigated. ***