Advancing Drug Development and Clinical Trials - Part 2 of a Monoclonol Antibody Characterization Series

[karen-thorson]

I’d like to start off with one powerful example of why immunotherapy work is so important. The story comes from Ron Levy’s work to use antibodies to fight lymphoma. One moving case describes a 36 year old woman from Texas with three children who in 1990 discovered a lump in her groin. A lymph node biopsy indicated Stage III follicular Lymphoma. Over the years, post diagnosis, this woman had short remissions after chemotherapy, radiation therapy and mAb therapy.  She had re-treatments of the mAb therapy and saw complete response for seven years at which time she went on a maintenance dose of the mAb again with remission. She is a 25-year cancer survivor. See more details on this patient and others in the video Monoclonal Antibodies: Stanford Academia-Industry Collaboration.

To get mAbs into clinical trials and on the market, characterization of them is required.  Met oxidation is one of the critical quality attributes required to be closely monitored. It commonly occurs during the manufacture and processing of mAbs. The effect of oxidation in some cases leads to increase plasma clearance or cause aggregation of the biopharmaceutical leaving it ineffective or even toxic. An example of the significance of oxidation is well described in the article by J Stracke et al PCM4622569.

The Thermo Scientific™ mAbPac™ RP has been shown to characterization of oxidation variants in recent chromatographic methods.  This is helping scientist move discovery and development of these beneficial drugs quickly through the process. Watch the video for a full summary of BioLC columns available for specific characterization issues.

The effort to combine the appropriate instruments, software, columns and techniques is now surmountable. If you are struggling with developing methods or finding columns that will aid your mAb characterization, there are chromatographic resources. Analytical workflows for Peptide Mapping, analysis of glycans, Intact protein, antibody drug conjugates, oligonucleotides and amino acids are all  detailed.  These links simplify the challenge of biopharmaceutical analysis.

References:

Column Technology for Monoclonal Antibody Analysis
Monoclonal antibodies to treat cancer
Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human ...