Abstract
Background1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method.ResultsHere, we present a comprehensive molecular and immunological characterization of 1E10 produced by the two different production processes in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced 1E10 and bioreactor-obtained 1E10. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models.ConclusionsChanges in 1E10 primary structure like glycosylation; asparagine deamidation and oxidation affected 1E10 structural stability but did not affect the immune response elicited in mice and chickens when compared to 1E10 produced in mice.
Highlights
1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides
N-terminal pyroglutamic acid, Asn glycosylation and three deamidation sites common for 1E10-AF and ST, while oxidized methionine found only in 1E10-ST Primary structure was determined by mass spectrometry using both MALDI-TOF2 and ESI-QTOF for MS2 measurements
Effector functions of classic therapeutic monoclonal antibodies can be divided in Fab-dependent functions and Fc-dependent functions
Summary
1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. Anti-idiotype vaccination represents an innovative approach to target tumor-associated antigen-expressing cells. This approach comes directly from Jerne’s idiotypic network theory, which postulates that due to the huge potentiality for diversity of the immunoglobulin variable regions, the idiotype repertoire can mimic the universe of self and foreign epitopes [1]. NeuGc-containing gangliosides are attractive targets for cancer immunotherapy because these glycolipids are non-self antigens in humans [2,3] They have been detected in different human tumors by antibodies and chemical analysis [4,5,6]. For phase I and II clinical trials, mAb-1E10 was produced in mice ascites, a common practice in the 1990’s for small scale antibody production.
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