Statistics of the distribution of the abundance of molecules with various drug loads in maytansinoid antibody-drug conjugates.

Abstract

The maytansinoid antibody-drug conjugates (ADCs) in clinical development for cancer therapy each contain a derivative of the microtubule-targeting agent, maytansine, covalently attached to the antibody via an engineered linker. A sample of any of these conjugates contains molecules with different numbers of maytansinoid molecules, or "drug" loads, the relative abundance of which can be determined by mass spectrometry. We examined the accuracy of the Poisson distribution and the binomial distribution in predicting the relative abundance of species with different drug loads for three antibody-maytansinoid conjugates with different antibodies and linker-maytansinoid pairings. We used variance, calculated from the experimental mass distribution data, as the parameter to determine the optimal value n of the binomial distribution number of trials. The accuracy of the Poisson distribution in predicting distribution of the species abundance in these conjugates varied among the conjugates. In contrast, the accuracy of the binomial distribution was similar for all three conjugates and comparable to the best accuracy of the Poisson distribution, as supported by a paired t-test.

• Authors: Victor S Goldmacher, Godfrey Amphlett, Lintao Wang, Alexandru C Lazar
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 12 Issue 6 Pg. 1738-44 (Jun 01 2015) ISSN: 1543-8392 [Electronic] United States
• PMID: 25635630 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Immunoconjugates
• Maytansine

Topics

• Antibodies, Monoclonal, Humanized (chemistry, pharmacokinetics)
• Humans
• Immunoconjugates (chemistry, pharmacokinetics)
• Mass Spectrometry
• Maytansine (chemistry)
• Models, Statistical