Comparability Assessments of Process Changes Made during Development of Anti-Idiotype Vaccine  

作　　者：Kathya de la Luz-Hernández Yamilé Rabasa Raquel Montesinos Dasha Fuentes Julio Felipe Santo Tomás Orlando Morales Yadira Aguilar Blanca Pacheco Adolfo Castillo Ana Maria Vazquez 

机构地区：[1]Center of Genetic Engineering and Biotechnology, Havana, Cuba [2]National Center for Laboratory Animal Breeding, Havana, Cuba [3]Process Development Direction, INIM, Center of Molecular Immunology, Havana, Cuba

出　　处：《World Journal of Vaccines》2014年第1期24-32,共9页疫苗（英文）

摘　　要：Racotumomab monoclonal antibody is a murine anti-idiotypic antibody. This monoclonal antibody mimics N-glycolyl-GM3 gangliosides has been tested in several clinical trials Phase I/II for breast, melanoma and non-small cell lung cancer patients as an anti-idiotypic cancer vaccine. The early production process was performed in vivo from mice ascites fluid. This process was transferred to bioreactor-based method at pilot scale followed to the scale-up of the fermentation. In this work we present a comprehensive molecular characterization of racotumomab MAb produced by the two different production scales in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern and charge heterogeneity between racotumomab produced in both scales. Interestingly, these modifications had no significant impact on biological activity elicited in chickens. So, changes in primary structure like glycosylation, charge heterogeneity and oxidation did not affect biological activity of the vaccine.Racotumomab monoclonal antibody is a murine anti-idiotypic antibody. This monoclonal antibody mimics N-glycolyl-GM3 gangliosides has been tested in several clinical trials Phase I/II for breast, melanoma and non-small cell lung cancer patients as an anti-idiotypic cancer vaccine. The early production process was performed in vivo from mice ascites fluid. This process was transferred to bioreactor-based method at pilot scale followed to the scale-up of the fermentation. In this work we present a comprehensive molecular characterization of racotumomab MAb produced by the two different production scales in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern and charge heterogeneity between racotumomab produced in both scales. Interestingly, these modifications had no significant impact on biological activity elicited in chickens. So, changes in primary structure like glycosylation, charge heterogeneity and oxidation did not affect biological activity of the vaccine.

关 键 词：Comparability Studies MONOCLONAL ANTIBODY Cancer VACCINE Mass SPECTROMETRY 

分 类 号：R73[医药卫生—肿瘤]