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

融合细胞系（如杂交瘤）的不稳定性仍然是生产商业上重要的单克隆抗体的主要并发症。在以前的工作中，这些pi表明杂交瘤细胞的生产力下降是由于形成了一个非生产性细胞亚群，而不是整个细胞系的减弱。非生产性细胞不产生必需抗体重链（HC）。HC产生的损失可能是DNA丢失或突变或某种影响mRNA产生、调节或翻译的事件的结果。在这个建议中，dna丢失假说将被研究。＊＊＊

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. ***