Research offers new understanding related to effects of chemical conjugation on stability of ADCs

Wolfe Laboratories today announced the presentation of an abstract related to its research efforts surrounding antibody-drug conjugates (ADCs) at the 245^th National Meeting of the American Chemical Society, held April 7-11 in New Orleans. The abstract details how scientists at Wolfe Laboratories, along with their University of Kansas collaborators, have found that conjugation site heterogeneity in ADCs affects the overall surface charge, which can lead to variable and unpredictable pharmaceutical performance.

“The influence of payload on the physiochemical stability of Fc-conjugates”

Janet Wolfe, President of Wolfe Laboratories, said, "ADCs are a rapidly growing class of oncology therapeutics that are incredibly promising, yet complex. Given the complexity of ADCs, the ability to control and fully characterize the conjugation sites will enable streamlined and cost-effective ADC discovery and development and may positively affect a conjugate's development potential and commercial value. Wolfe is expanding its research efforts in this important area to better predict and control the pharmaceutical properties of ADCs. This type of research exemplifies our commitment to providing translational drug development solutions and actionable, meaningful information to our customers."

The physiochemical stability of ADCs during manufacturing, storage and administration is an important factor influencing their therapeutic efficacy; however, it has remained unclear how covalent modifications alter the stability of these conjugates. Wolfe Laboratories researchers utilized analytical methods such as size-exclusion chromatography, dynamic light scattering and ion exchange chromatography to characterize the size and charge of conjugates created through conjugating fluorophores to lysine residues in the constant (Fc) region of IgG1. This research offers new understanding related to the effects of chemical conjugation on the stability of ADCs, providing important information on the effects of drug-to-antibody ratio and fluorophore hydrophobicity on the stability of Fc-conjugates.