ABSTRACT
Freeze-thaw cycles impact the amount of aggregation observed in antibodies and Fc-fusion proteins. Various formulation strategies are used to mitigate the amount of aggregation that occurs upon putting a protein solution through a freeze-thaw cycle. Additionally, low pH solutions cause native antibodies to unfold, which are prone to aggregate upon pH neutralization. There is great interest in the mechanism that causes therapeutic proteins to aggregate since aggregate species can cause unwanted im-munogenicity in patients. Herein, an increase in aggregation is reported when the pH is adjusted from pH 3 up to a pH ranging from pH 4 to pH 7 during the thaw process of a frozen antibody solution. Raising the pH during the thaw process caused a significant increase in the percent aggregation observed. Two antibodies and one Fc-fusion protein were evaluated during the pH jump thaw process and similar ef-fects were observed. The results provide a new tool to study the kinetics of therapeutic protein ag-gregation upon pH increase.
ABSTRACT
Se analizaron 47 pacientes operados por carcinoma mamarioo que concurrían a control a la Unidad de Patología Mamaria del HZGA San Roque de Gonnet. Se evaluó la calidad de vida, por medio de instrumentos estandarizados: MMS, SCL-90 y PS Kamolsky index. Las enfermas se separaron en grupos considerados cinco variables: edad, tipo de cirugía, tiempo desde la cirugía, estado civil y estado menopáusico. No se encontraron diferencias al nivel de significación de p= 0,05. Analizada la muestra en conjunto y comparada a una muestra de población de mujeres no pacientes, el 44,7 por ciento de las enfermas fueron consideradas casos o diagnósticos positivos. Se podría concluir que estas pacientes presentan un elevado nivel de distress comparadas a una muestra estándar, pese a no haberse identificado diferencias significativas en las variables analizadas