Materials Processing Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16606-11. doi: 10.1073/pnas.1112241108. Epub 2011 Sep 15.
We report the observation of liquid-liquid phase separation in a solution of human monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude of the effective interprotein interactions. Our analysis suggests that additives (HSA in this report), which have moderate attraction with antibody molecules, may be used to forestall undesirable protein condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia.
我们报告了人源单克隆抗体 IgG2 溶液中液-液相分离的观察结果，以及主要血液蛋白人血清白蛋白对这种相分离的影响。我们发现白蛋白的存在显著降低了相分离温度，并且白蛋白优先分配到富含抗体的相中。我们提供了抗体-白蛋白混合物相图的一般热力学分析，并将其特征与有效蛋白间相互作用的大小联系起来。我们的分析表明，具有中等吸引力的添加剂（本报告中的 HSA）可用于防止抗体溶液中不希望的蛋白质凝聚。我们的发现与理解抗体药物溶液的稳定性和冷球蛋白血症的机制有关。
